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On 20 September, Alvotech announced that the FDA has accepted its resubmitted Biologics License Application (BLA) for AVT02, a high-concentration, interchangeable biosimilar to AbbVie’s Humira® (adalimumab). The BsUFA goal date for the resubmitted BLA is 24 February 2024. Alvotech stated that the FDA indicated that the resubmission, which incorporated additional Chemistry, Manufacturing, and Controls information, is considered to be a completed response to the FDA’s Complete Response Letter (CRL) of 28 June 2023. Alvotech announced on 13 April 2023 that it had responded to an earlier CRL received in March 2023.
On 31 August 2023, Alvotech announced that it had resubmitted the BLA for AVT02 to the FDA but did not disclose details or the BsUFA goal date.
KED Global reported that Celltrion won bids to supply Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab), in five regions of Italy – accounting for approximately 20% of the Italian adalimumab market. Yuflyma® recorded ₩54B (USD$40.7M) of sales in the first half of 2023, which Celltrion says is due to its expansion into Europe.
On 11 May 2023, Celltrion won bids to supply Vegzelma® (bevacizumab) in Italy and Belgium.
According to the Pharmaceutical Benefits Assessment Committee (PBAC) November 2023 agenda published last week, the meeting will be jammed with biopharma applications for reimbursement. PBAC will consider the following applications for PBS listing additions or amendments at its November 2023 meeting:
|New listing applications:||Amendment Applications|
|1. Organon’s Hadlima® (adalimumab) biosimilar to AbbVie’s Humira®||1. Sanofi-Aventis’ Libtayo® (cemiplimab)|
|2. GSK’s Jemperli® (dostarlimab)||2. BMS’s Opdivo® (nivolumab)|
|3. Vertex’s Kalydeco® (ivacaftor)||3. Merck’s Keytruda® (pembrolizumab)|
|4. GSK’s Menveo® (meningococcal vaccine)||4. AbbVie’s Skyrizi® (risankizumab)|
|5. Pfizer’s Prevenar 20® (pneumococcal conjugate vaccine)||5. Novartis’ Cosentyx® (secukinumab)|
|6. Generic Health’s Teriparatide Lupin® (teriparatide) biosimilar to Eli Lily’s Forteo®|
|7. Gedeon Richter’s Terrosa® (teriparatide) biosimilar to Eli Lily’s Forteo®|
|8. Beigene’s Tevimbra® (tiselizumab)|
|9. AstraZeneca’s Enhertu® (trastuzumab deruxtecan) biosimilar to Genentech’s Herceptin®|
In addition, a number of PBAC recommendations not accepted by applicants are set for review, including relating to Alphapharm’s Hulio® (adalimumab, biosimilar to AbbVie’s Humira®), Pfizer’s Zirabev® (bevacizumab, biosimilar to Genentech’s Avastin®) and Alphapharm’s Rymti® (etanercept) biosimilar to Amgen’s Enbrel®.
On 1 March 2023, the November 2022 PBAC outcomes were announced, with three biologics listed, including Sanofi-Aventis’ dupilumab (Dupixent®) autoinjectors in two new forms, Merck’s pembrolizumab (Keytruda®) and AbbVie’s risankizumab (Skyrizi®).
Alvotech announced in its 2023 Q2 Earnings Presentation that it has resubmitted its interchangeable BLA for AVT02, biosimilar to AbbVie’s high concentration Humira® (adalimumab). The company did not disclose the BsUFA date but anticipated launch in 2024.
The FDA issued a complete response letter (CRL) for Alvotech’s interchangeable BLA on 28 June 2023, noting issues at Alvotech’s facility in Reykjavik, Iceland.
Alvotech also reported that AVT04, its biosimilar to Stelara®, is filed and pending approval in 7 markets including U.S, EU, Japan, and Canada, and it is expecting some approvals to occur before end of 2023.
Alvotech published its financial results on 30 August 2023.
Celltrion Healthcare Canada announced that Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab), is now available in an 80 mg auto-injector and pre-filled syringe. It is the only adalimumab biosimilar available at an 80 mg dose in an auto-injector.
Alvotech and Bioventure announced that AVT02, their biosimilar to AbbVie’s Humira® (adalimumab) has been approved (under brand name Adalimumab-EVA®) by the Egyptian Drug Authority. Bioventure is Alvotech’s exclusive strategic partner for the commercialisation of AVT02 and other biosimilars in the Middle East and North Africa.
On 24 January 2023, Alvotech and Bioventure announced that the Saudi Food & Drug Authority has approved the manufacture and distribution of AVT02 under the brand name Simladi®.
Teva’s CEO confirmed that it will still pursue launching its Alvotech developed adalimumab biosimilar of AbbVie’s Humira® (adalimumab) next year despite seven biosimilars launching in the US on 1 July 2023, and Amgen launching Amjevita® on 31 January 2023. Teva’s CEO, Richard Francis noted that “it’s always going to be a challenging market but I do see it’s worth the effort for 2024.”
On 24 July 2023, Teva and Alvotech announced they agreed to expand their existing strategic partnership agreement for the US, which already included development of AVT02 (adalimumab).
Samsung Bioepis and Organon announced the topline results for their interchangeability study for SB5 (Hadlima®), a biosimilar to AbbVie’s Humira® (adalimumab). The Phase 4, randomized, double-blind, parallel-group, multiple-dose, active comparator, multicenter clinical study (NCT05510063) was in patients with moderate to severe chronic plaque psoriasis. The study found that efficacy profiles, safety profiles and immunogenicity were comparable between patients who received Hadlima® and those who received Humira®.
Prime Therapeutics announced its 2023 recommendations for formularies that include AbbVie’s Humira® (adalimumab). The pharmacy benefit manager will recommend coverage of the following adalimumab biosimilars to commercial clients:
- Amgen’s Amjevita® (low concentration) and Boehringer Ingelheim’s Cyltezo® (interchangeable low concentration); or
- Amgen’s Amjevita® (low concentration) and Samsung Bioepis/Organon’s Hadlima® (high and low concentration).
Prime is also recommending coverage of Cyltezo® for Medicare Part D formularies. On 10 July 2023, Cigna Health announced its preferred adalimumab biosimilars.
Cigna Healthcare, a pharmacy manager, announced it will prefer adalimumab biosimilars Boehringer Ingelheim’s Cyltezo®, Sandoz’s unbranded adalimumab-adaz, and Sandoz’s Hyrimoz high-concentration formulation alongside the originator product, Abbvie’s Humira® on its national preferred, standard, performance, and legacy commercial formularies. Organon/Samsung Bioepis’ Hadlima®, in both high- and low-concentration formulations, will be preferred alongside Humira® on its value, advantage, and total savings formularies. The announcement will be effective from 1 September 2023.
In the first week of July 2023, seven biosimilars to AbbVie’s Humira® were made commercially available in the US.
Organon and Samsung Bioepis announced that Hadlima®, biosimilar to AbbVie’s Humira® (adalimumab), is now available in the US. Hadlima® is available at a list price of $1,038, an 85% discount in comparison to the list price of Humira®.
On 1 July 2023, the following biosimilar entities are licensed to launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi in July (on an unspecified date), Mylan/Viatris on 31 July 2023, Sandoz on 30 September 2023, Momenta and Pfizer on 20 November 2023.
Seven biosimilars to AbbVie’s Humira® (adalimumab): Coherus Biosciences’ Yusimry®, Organon and Samsung Bioepis’ Hadlima®, Sandoz’s Hyrimoz®, Celltrion’s Yuflyma®, Fresenius Kabi’s Idacio®, Biocon Biologics’ Hulio® and Boehringer Ingelheim’s Cyltezo® are now commercially available in the US.
Each became authorised for supply in the US in July 2023 following their respective settlements with AbbVie. Samsung Bioepis settled with AbbVie on 5 April 2018, Viatris settled on 17 July 2018 (Biocon acquired Viatris’ global biosimilars business in November 2022), Sandoz settled on 11 October 2018, Fresenius settled on 18 October 2018, Boehringer settled on 14 May 2019, and Coherus settled on 27 November 2019, and Celltrion obtained a licence from AbbVie on 27 April 2022.
AbbVie entered into other deals with biosimilar entrants enabling US market entry, including: Alvotech (market entry on 1 July 2023, which has been delayed by a recent CRL from the FDA), Momenta (market entry on 20 November 2023), and Pfizer (market entry on 20 November 2023).
Alvotech provided an update about its high concentration adalimumab (AVT02) application in the US. Alvotech has announced that the FDA issued a complete response letter (CRL) for its second BLA for AVT02 (high-concentration adalimumab, biosimilar to AbbVie’s Humira®, with interchangeability designation). The CRL highlighted certain deficiencies found during the FDA’s reinspection of Alvotech’s facility in Reykjavik, Iceland must be resolved before the AVT02 application can be approved. Alvotech will now submit a new BLA for AVT02, with data supporting its interchangeability designation. Alvotech is exploring options to raise additional capital “due to the expected delay in the potential approval of AVT02 in the US”.
On 13 April 2023, Alvotech announced that had received and responded to the first CRL from the FDA regarding AVT02. From 1 July 2023, Alvotech is licensed to supply AVT02 in the US from 01 July 2023 in accordance with its licence agreement with AbbVie.
Boehringer Ingelheim announced that Optum Rx, pharmacy benefit manager, will place Cyltezo® (adalimumab-adbm), the FDA-approved Interchangeable biosimilar to AbbVie’s Humira® on its commercial formulary as a preferred brand. Optum Rx covers more than 66 million members in the US.
Optum Rx will also supply two other adalimumab biosimilars, Sandoz’s Hymiroz® and Amgen’s Amjevita®
Cyltezo® became authorised for supply in the US on 1 July 2023 following the Boehringer and AbbVie settlement of their patent dispute on 14 May 2019.
Coherus has confirmed in a Form 8-K filed with the SEC that it has resolved its recent dispute with AbbVie relating to a potential breach of its settlement and licence agreement entered into in late 2019, under which Coherus received a royalty bearing non-exclusive licence to commercialise its biosimilar adalimumab YUSIMRY® from 1 July 2023.
According to the SEC disclosure, in a letter from AbbVie Coherus received on 6 June 2023, AbbVie claimed that Coherus breached its obligations under the agreement by announcing an 85% discount for its US launch of YUSIMRY® and its partnership with Mark Cuban on 1 June 2023.
Coherus responded to AbbVie on 11 June 2023 denying the allegation and requesting more information. On 13 June, it also filed a motion for a temporary restraining order in the District Court of Delaware against AbbVie to prevent it from terminating the license, and AbbVie filed for preliminary injunction on the same day
After negotiations the next day, 14 June 2023, Coherus agreed to resolve its motion for a temporary restraining order against AbbVie, and AbbVie agreed not to terminate the licence agreement relating to the commercialisation of YUSIMRY®, adalimumab biosimilar to AbbVie’s Humira®. AbbVie will only be entitled to terminate if it serves a new notice of breach and affords Coherus an opportunity to cure any alleged breach.
Rani Therapeutics announced that it has expanded its partnership with Celltrion to develop an orally administered adalimumab biosimilar RT-105, following their previous collaboration on an ustekinumab biosimilar. The partnership allows Rani to use Celltrion’s adalimumab biosimilar drug substance (CT-P17) exclusively for the development and commercialisation of RT-105. Celltrion will have the option to acquire worldwide rights to RT-105 after a phase I study.
Rani developed the RaniPill® capsule, an oral delivery technology which intends to replace subcutaneous or intravenous injection of biologics and drugs. This is the first announced partnership for a program involving the RaniPill® HC, a high-capacity device in preclinical testing that delivers 20mg of payload with high bioavailability.
Coherus announced it is launching YUSIMRY® (adalimumab-aqvh) biosimilar to AbbVie’s Humira®, in July 2023 with a list price of $995 per carton. This is the lowest price announced of any adalimumab product in the US, and represents an 85% discount on the originator product.
On the same day, Coherus also announced a partnership with Mark Cuban Cost Plus Drug Company (MCCPDC) to offer MCCPDC customers YUSIMRY® in July 2023 for $569.27 plus dispensing and shipping fees.
YUSIMRY® was approved by the FDA in December 2021 indicated for plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis. As the AbbVie global Humira® (adalimumab) empire crumbles, Samsung Bioepis/Merck has the next licensed launch date in the US on 30 June this year, and the next day (1 July) the following biosimilar entities are licensed launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi in July (on an unspecified date), Mylan/Viatris on 31 July 2023, Sandoz on 30 September 2023, Momenta and Pfizer on 20 November 2023.
A study published in JAMA Network Open has found in a systematic review and meta-analysis that biosimilars of adalimumab, etanercept, and infliximab were associated with clinically equivalent effects in patients with rheumatoid arthritis compared with their reference biologics (AbbVie’s Humira®, Amgen’s Enbrel® and J&J’s Remicade® respectively). The authors assessed 25 head-to-head trials (including 10,642 randomised participants) and found the biosimilars were associated with similar rates of adverse events, study discontinuation, and immunogenicity responses compared with reference biologics.
Only two weeks ago on 8 June 2023, the Ph III results of Samsung Bioepis’ SB15 (aflibercept biosimilar) published in JAMA Ophthalmology showed equivalent efficacy and comparable safety, pharmacokinetics and immunogenicity to reference aflibercept.
Celltrion announced that its Yuflyma® (adalimumab) product, a high-concentration formulation and biosimilar to AbbVie’s Humira®, has obtained FDA approval. According to Celltrion, Yuflyma® will be available in the US from July for the key indications of Humira®, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and Hidradenitis Suppurativa.
Celltrion’s announcement came only three days after Boehringer Ingelheim announced its Humira® biosimilar Cyltezo® autoinjector pen obtained FDA approval.
Boehringer Ingelheim announced that the FDA has approved an autoinjector pen presentation of its Cyltezo® (adalimumab-adbm), an FDA-approved interchangeable biosimilar to AbbVie’s Humira® (adalimumab). Cyltezo® is indicated for multiple chronic inflammatory diseases. The autoinjector pens will be available in the US from 1 July 2023.
Boehringer is licensed to supply its adalimumab biosimilar in the US from 1 July 2023. In total, AbbVie entered into numerous deals with biosimilar entrants enabling US market entry as follows: Samsung Bioepis/Merck (30 June 2023), Alvotech (1 July 2023), Coherus (1 July 2023), Celltrion (July 2023), Fresenius Kabi (July 2023), Mylan/Viatris (31 July 2023), Sandoz (30 September 2023), Momenta (20 November 2023), and Pfizer (20 November 2023).
Alvotech has provided updates on some of its biosimilar products in its report on its financial results for the first 3 months of 2023.
- As previously reported, Alvotech initiated a confirmatory patient study for AVT05, its proposed biosimilar to Simponi® and Simponi Aria® (golimumab).
- In March 2023, Alvotech provided Biosana Pharma a notice of termination for the licensing agreement between the two companies relating to AVT23, biosimilar to Xolair® (omalizumab). The deal was announced in February 2022.
Alvotech announced that it received (in March) and responded to (in April) a complete response letter from the FDA regarding its BLA for high concentration (buffer free) formulation of AVT02, biosimilar to AbbVie’s Humira®, and is awaiting the FDA’s assessment of its response.
Alvotech has filed a second BLA for AVT02, which contains data to support approval as a biosimilar with interchangeability designation. This remains under review by the FDA, with a BsUFA date of 28 June 2023.
Satisfactory outcome of the facility reinspection remains the key requirement for approval of both ABLAs.
Sandoz announced that the EC granted marketing authorisation in the EU for its citrate-free high concentration (100mg/ml) formulation of its Hymiroz® (adalimumab), biosimilar to AbbVie’s Humira®, for all indicates covered by Humira®.
On 21 March 2023, the Sandoz citrate-free high concentration formulation of adalimumab Hymiroz® was approved by the FDA. Sandoz intends to launch in the US on 1 July 2023 pursuant to its 2018 settlement with AbbVie.
The PBS Catch-up Statutory Price Reductions have reduced the cost of AbbVie’s Humira® products by 24.39% to $618.90, with adalimumab biosimilars (Arrow Pharma’s Hadlima®, Apotex’ Amgevita®, Sandoz’ Hyrimoz® and Fresenius Kabi’s Idacio®) reduced by 6.91%. Interestingly, this means that the originator AbbVie Humira® product will have a lower PBS reimbursement price than equivalent biosimilars.
As the AbbVie global Humira® empire crumbles, Samsung Bioepis/Merck has the next licensed launch date in the US on 30 June this year, and the next day (1 July) the following biosimilar entities are licensed to launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi in July (on an unspecified date) and, Mylan/Viatris on 31 July 2023.
Last week we reported the FDA approved Sandoz’ adalimumab biosimilar Hyrimoz®; and two weeks ago we noted that AbbVie owes US Medicare rebates to the Centers for Medicare & Medicaid Services for raising the price of Humira® faster than inflation.
Two biosimilars are on the July 2023 PBAC meeting agenda seeking to be PBS reimbursed for Australia:
- Cipla Australia has applied to list Ardalicip®, biosimilar to AbbVie’s Humira® (adalimumab), which was developed by Alvotech (AVT02)
- Juno Pharmaceuticals has applied to list Exarane™ and Exarane Forte™ (Sanofi’s Lovenox®) (enoxaparin)
A study published in Clinical and Experimental Rheumatology found that patients with rheumatoid arthritis and psoriatic arthritis (PsA) experienced a worsening in the patient global assessment when they switched from AbbVie’s Humira® (adalimumab) to Samsung Bioepis’ Imraldi® for administrative/economic reasons. Patients with PsA also reported a worsening in Health Assessment Questionnaires. However, there were no differences found in other relevant scores (such as the disease activity score or Bath Ankylosing Spondylitis Disease Activity Index). Interestingly, where patients switched (also for non-medical reasons) from Amgen’s biosimilar Amgevita® to Imraldi®, no differences were found in patient-reported outcomes.
The authors concluded that these results may be due to a possible nocebo response, and encouraged comprehensive communication with patients to prevent worse outcomes when switching from the originator product to a biosimilar.
Sandoz announced that it has received FDA approval for its Hyrimoz® (adalimumab), biosimilar to AbbVie’s Humira® in a citrate-free, high concentration formulation that it intends to launch in the US on 1 July 2023 pursuant to the licence granted in its settlement with AbbVie on 11 October 2018. Hyrimoz® is approved for the same seven indications as the reference product, AbbVie’s Humira®.
This follows Amgen’s recent launch of Amjevita®, the first adalimumab biosimilar available in the US on 31 January 2023 pursuant to its AbbVie settlement dated 28 September 2017. In total, AbbVie entered into 11 deals with biosimilar entrants enabling US market entry as follows: Amgen (31 January 2023), Alvotech (1 July 2023), Celltrion (July 2023), Mylan/Viatris (31 July 2023), Sandoz (30 September 2023), Momenta (20 November 2023), Pfizer (20 November 2023), Fresenius Kabi (July 2023), Samsung Bioepis/Merck (30 June 2023), Coherus (1 July 2023) and Boehringer Ingelheim (1 July 2023).
The US Department of Health and Human Services and the White House have announced that AbbVie will be required to pay rebates to the Centers for Medicare & Medicaid Services for raising the price of Humira® (adalimumab) faster than inflation. This new mechanism was brought about by the Inflation Reduction Act 2022 through the Medicare Prescription Drug Inflation Rebate Program. This new inflation rebate applies to Medicare Part B rebatable drugs: single source drugs, biological products and certain biosimilars.
MiGenTra, a German healthcare transforming company, announced the commencement of the German phase I trial of Minapharm Pharmaceuticals’ African developed adalimumab biosimilar (Adessia®) on 24 February 2023. Results are expected at the end of 2023.
MiGenTra was founded in 2021 by ProBioGen (CMDO) and Minapharm Pharmaceuticals with management in Berlin and Cairo, to develop biosimilars, cell and gene therapies and vaccines. MiGenTra and Minapharm Pharmaceuticals are jointly responsible for filing and commercialising Adessia® in Africa and the Middle East.
A Turgut İlaçları study published in the Turkish Journal of Pharmaceutical Sciences indicated that Turgut’s TUR01, biosimilar to Amgen’s Humira® (adalimumab), was stable when stored under long-term storage conditions at for at least 18 months and for 24 months. In 2020, Turgut completed a phase I study to compare the pharmacokinetics, safety, tolerability, and immunogenicity of two formulations of adalimumab (TUR01 and EU Sourced Humira®). The results have not been disclosed.
Despite eight adalimumab biosimilar products available in the US, on 3 August 2023 Teva confirmed its intention to launch its AVT02 adalimumab biosimilar in 2024.
Alvotech announced its full financial results for 2022, highlighting its annual revenue increased by 114% to USD$85M, primarily driven by the commercialisation of AVT02 (adalimumab), biosimilar to AbbVie’s Humira® in 17 countries. As of December 31, 2022, the company had cash and cash equivalents of US$66.4 million, and R&D expenses were US$180.6 million. In addition, Alvotech highlighted recent corporate achievements, including its marketing applications for AVT04 (ustekinumab), a proposed biosimilar to Johnson & Johnson’s Stelara® in the US (FDA accepted BLA for review in January 2023 with a new goal date of 13 April 2023), and EU (expected EMA recommendation in the second half of 2023).
The company held a business update conference with the investment community on 2 March 2022.
Robert Wessman, Chairman and CEO of Alvotech said that “Looking ahead, 2023 is expected to be equally important. We’re currently preparing for a reinspection of our Reykjavik facility by the FDA, which, if satisfactory, could pave the way for the approval and subsequent launch of our interchangeable, high concentration biosimilar to Humira® in the US market on July 1, 2023.”
Biospectrum India reported that Enzene Biosciences has launched its adalimumab (biosimilar to AbbVie’s Humira®) in India for the treatment of ankylosis spondylitis and rheumatoid arthritis. Enzene believes that this is the first commercial launch using continuous manufacturing technology, which will reduce COGS. This is the fourth biosimilar launch for Enzene, following teriparatide (treatment for osteoporosis) approval on 4 February 2021, romiplostim (treatment for chronic Immune Thrombocytopenic Purpura) on 10 August 2021, and denosumab (treatment for osteoporosis) on 27 August 2021.
The Korea Biomedical Review has reported that Celltrion has explained to shareholders the delay in obtaining US approval for its Humira® adalimumab biosimilar Yuflyma®. Despite obtaining EMA approval in December 2020, Celltrion confirmed that FDA took issue with Celltrion’s overseas and end-product manufacturing plants. Celltrion has rectified the problems and the FDA will complete a final review by May 2023. We have previously reported on Yuflyma®’s progress and approvals including its EU approval in December 2020, in CA on 24 December 2021 and in AU on 28 February 2022. Celltrion is licensed to supply Yuflyma® in the US from July 2023 pursuant to its settlement with AbbVie.
The Financial Times has reported that the Dutch Pharmaceutical Accountability Foundation (PAF), a public interest group, is suing Abbvie for allegedly overcharging citizens for Humira® (adalimumab) in Holland. PAF is arguing that the pricing of the drug is in breach of human rights. AbbVie has rejected the allegations
Growth Plus Reports has reported that the adalimumab global biosimilars market (valued at US$3.53B in 2021) and is expected to reach US$18.53B by 2030. The report notes that Europe is the key growth region for the adalimumab global biosimilars market, and Amgen’s Amjevita® to AbbVie’s Humira® has the largest market share.
Read our previous post about the short term US cost savings expected from Amjevita® here.
Biora Therapeutics announced preliminary results from preclinical testing of PGN-0B1, reporting an average bioavailability greater than 50% for a variant of adalimumab. Biora’s systemic therapeutics platform uses an ingestible capsule for needle-free, oral delivery of biotherapeutics using liquid jet delivery.
Organon published its results for Q4 and full year ended 31 December 2022, reporting a second consecutive year of double-digit revenue growth in biosimilars. Organon reported that this growth was primarily drive by double-digit growth from Renflexis® (biosimilar to Johnson & Johnson’s Remicade® infliximab), Ontruzant® (biosimilar to Roche’s Herceptin® trastuzumab), Hadlima® (biosimilar to AbbVie’s Humira® adalimumab) and Aybintio® (biosimilar to Roche’s Avastin bevacizumab).
Reuters reported that it expects only limited cost savings to result from Amgen’s launch of Amjevita® (biosimilar to AbbVie’s Humira® adalimumab) in the US in January this year. Reuters reported that while Amgen launched Amjevita at two price points (one with a 5% discount to Humira, and one with a 55% discount to Humira), the more heavily discounted product is not expected to be as widely used.
Costs may ease later this year with the launch of biosimilars developed by Alvotech (1 July 2023), Celltrion (July 2023 – but Celltrion’s launch may be delayed as reported above), Mylan/Viatris (31 July 2023) Sandoz (30 September 2023), Momenta (20 November 2023) Pfizer (20 November 2023), Fresenius Kabi (July 2023), Samsung Bioepis/Merck (30 June 2023), Coherus (1 July 2023) and Boehringer Ingelheim (1 July 2023).
The much anticipated launch of the first US Humira biosimilar occurred with Amgen launching Amjevita® (adalimumab) on 31 January 2023, pursuant to its settlement agreement with AbbVie which was penned in September 2017. Amjevita® is the first adalimumab biosimilar to be launched in the US and is available at a Wholesale Acquisition Cost 55% below the current Humira® list price. Biosimilars developed by Alvotech, Celltrion, Mylan/Viatris, Sandoz, Momenta, Pfizer, Fresenius Kabi, Samsung Bioepis/Merck, Coherus and Boehringer Ingelheim are able launch in the US later this year, in accordance with their settlements with AbbVie.
On 16 September 2022 Pearce IP prepared a Vlog in its PiPCast® series on IP strategies to enable the launch of biosimilars around the world, with a particular focus on Australia.
A CVS report has predicated that interchangeability designations for adalimumab biosimilars will not primarily drive their adoption by prescribers. This contradicts the Cardinal Health 2023 Biosimilars Report, which found that a majority of providers intended to only prescribe interchangeable adalimumab biosimilars, rather than AbbVie’s Humira®.
Earlier in January 2023, we reported that Samsung Bioepis was accelerating its interchangeability studies for Hadlima® (adalimumab biosimilar). In December 2022, Alvotech announced that the FDA confirmed that data supplied for its AVT02 (adalimumab biosimilar) was sufficient to support a determination of interchangeability.
The CHMP adopted a positive opinion recommending the approval of a citrate-free high concentration formulation of Hyrimoz® (adalimumab), biosimilar to AbbVie’s Humira®. The positive opinion relates to all indications in the reference product, Humira®. Hyrimoz was first approved in the EU in July 2018, and Sandoz is seeking to expand its approved indications to those of Humira.
Alvotech and Bioventure announced that the Saudi Food & Drug Authority has approved the manufacture and distribution of Simladi™ (AVT02, biosimilar adalimumab). Bioventure, is a wholly owned subsidiary of GlobalOne Healthcare Holding LLC, the healthcare division of Yas Holding LLC, and is Alvotech’s exclusive strategic partner for the commercialisation of Simlandi in the Middle East and North Africa.
Samsung Bioepis announced that Health Canada has approved its high concentration, citrate-free (100mg/mL) Hadlima® (biosimilar adalimumab) following FDA approval in August 2022.
The Korea Herald reported that Samsung Bioepis has brought forward its interchangeability study of Hadlima® (biosimilar adalimumab). Samsung had previously announced that it would complete the study by September 2023, however now plans to complete the study in May 2023. Samsung reported that Organon will launch in the US by July 2023 in accordance with its settlement agreement with AbbVie, without an interchangeable designation.
Alvotech announced that the FDA has granted a new Biosimilar User Fee Amendment goal date of 13 April 2023 for its AVT02 (biosimilar adalimumab), and that FDA has confirmed that the data provided are sufficient to support a determination of interchangeability, subject to a site reinspection. Alvotech is licensed to supply AVT02 in the US from 01 July 2023 in accordance with a licence agreement with AbbVie.
Ontario announced that it will adopt a biosimilars switching program from 31 March 2023. Patients currently treated with Copaxone® (glatiramer acetate), Enbrel® (etanercept), Humalog® (insulin lispro), Humira® (adalimumab), Lantus® (insulin glargine), NovoRapid® (insulin aspart), Remicade® (infliximab), and Rituxan® (rituximab) will be required to transition to the biosimilar version by 29 December 2023. Ontario is the 8th jurisdiction to adopt a biosimilars switching program, following British Columbia, Alberta, New Brunswick, Quebec, Northwest Territories, Nova Scotia and Saskatchewan.
Fresenius Kabi announced that the FDA has approved its citrate-free biosimilar adalimumab (Idacio®) for all Humira® indications. Idacio was approved in the EU 2019. Fresenius intends to launch in the US in July 2023 pursuant to its settlement agreement with AbbVie.
Alvotech and STADA announced the launch of their high-concentration, citrate free biosimilar adalimumab Hukyndra® in Belgium, Bulgaria, Croatia, Czech Republic, Latvia, Romania, and Slovenia. Hukyndra was first launched in Europe in June 2022, and in Switzerland in September 2022. STADA has commercialisation rights to Hukyndra under a November 2019 strategic agreement with Alvotech.
Junshi Biosciences announced today that China’s NMPA has approved its supplemental application for additional indications for 君邁康® (biosimilar adalimumab) for the treatment of Crohn’s disease, uveitis, polyarticular juvenile idiopathic arthritis, plaque psoriasis in children and Crohn’s disease in children.
Korea Biomedical Review reported that Celltrion has obtained approval from South Korea’s Ministry of Food and Drug Safety for a domestically manufactured Yuflyma® (biosimilar adalimumab).
Alvotech announced the Australian approval for AVT02 (biosimilar adalimumab). Cipla will supply Alvotech’s product in Australia and New Zealand under a partnership first announced in July 2019 for adalimumab, which was expanded in March 2021 to include 4 additional biosimilars: aflibercept, ustekinumab, denosumab and golimumab biosimilars.
Alvotech announced that it will present two posters (and will be featured in an Ignite Talk) related to its switching study for ATV02 (100mg/mL citrate-free biosimilar adalimumab) at the American College of Rheumatology (ACR) Convergence Conference, in Philadelphia on November 10-14, 2022. Alvotech is the only known company that has both developed a high-concentration biosimilar candidate to Humira and completed a switching study to support potential regulatory approval as an interchangeable product. Alvotech’s application for AVT02 was accepted in February 2022.
Amgen announced that it will present data across its portfolio at the American College of Rheumatology Convergence on 10-14 November 2022, including data for Amgevita® (biosimilar adalimumab), Enbrel® (biosimilar etanercept) and Prolia® (biosimilar denosumab).
The Australian Pharmaceutical Benefits Advisory Counsel (PBAC) published the public summary documents from its July 2022 meeting. Among the updates were:
- Yuflyma® (adalimumab): recommended with ‘a-flagged’ status for the same indications as Humira®.
- Tysabri® (natalizumab): amended listings (removing a requirement for neurologists prescribing natalizumab to be registered with the Tysabri Australian Prescribing Program) recommended by PBAC.
- Epidyolex® (cannabidiol): not recommended for the treatment of Lennox-Gastaut syndrome, as the incremental cost effectiveness ratio was deemed to be unacceptably high at the price proposed.
- Keytruda® (pembrolizumab): amended listings (increasing the max number of repeats, and maximum number of cycles in a lifetime) recommended by PBAC.
- Stelara® (ustekinumab): vial for IV infusion and PFS recommended for the treatment of moderate to severe ulcerative colitis. 90mg/1mL PFS recommended for the treatment of Crohn disease and severe chronic plaque psoriasis.
In an interview with Managed Healthcare, Samsung Bioepis’ head of US market access Tom Newcomer announced that Samsung Bioepis will pursue interchangeability for Hadlima® (biosimilar adalimumab) in 2024. Hadlima was approved in the US in July 2019 and is expected to launch in the US from July 2023 pursuant to an agreement with AbbVie.
Celltrion announced the commencement of Ph III clinical trials regarding Yuflyma® (biosimilar adalimumab) in Estonia. This trial will run for 13 months and will be used to support Celltrion’s application for interchangeability in the US. Yuflyma was approved in the EU in February 2021, and in Canada in December 2021.
Alvotech and STADA announced the launch of Hukyndra® (100mg/mL, citrate free biosimilar adalimumab) in Switzerland. Alvotech reached a settlement with AbbVie in April 2022, enabling the launch of adalimumab across Europe, and STADA has since launched Hukyndra in several European countries from June 2022. Alvotech and STADA announced an exclusive partnership in November 2019 relating to six biosimilars, including adalimumab.
Australia’s TGA approved Cipla/Alvotech’s 100mg/mL adalimumab biosimilar AVT02 (Ciptunec®/Ardalicip®) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, hidradenitis suppurativa and uveitis. Cipla will supply Alvotech’s product in Australia and New Zealand under a partnership first announced in July 2019, which was expanded in March 2021 to include aflibercept, ustekinumab, denosumab and golimumab biosimilars.
Alvotech published its first half 2022 financial results, reporting a revenue growth to over $40 million compared to $2.0 million in the first half of 2021 due to recent launches of adalimumab (AV02) in Canada and Europe. The company has $128.4Min cash/equivalents and has current borrowings of $120.8M. Its R&D costs in the same period were 86.9M.
Alvotech “pipeline highlights” includes (amongst other things) an exclusive global licence agreement with BiosanaPharma regarding biosimilar omalizumab/to Xolair®, expanded partnership with Fuji Pharma, the completion and US submission of interchangeability studies for its high concentration adalimumab biosimilar, a US settlement with AbbVie relating to adalimumab and positive results from clinical studies on AVT04 (biosimilar ustekinumab/Stelara®). Alvotech also secured funding of approximately $185M through the OACB merger and PIPE financing.
STADA published its first half 2022 financial results, reporting a 15% increase in adjusted group sales. Adjusted for currency fluctuations and special effects, earnings before interest, tax, depreciation and amortisation (EBITDA) improved by 23% to €386.5 million. STADA currently markets five biosimilar products, including Hukyndra® (biosimilar adalimumab) and Oyavas® (biosimilar bevacizumab).
Samsung Bioepis and Organon announced that the FDA has approved the citrate-free, high-concentration (100mg/mL) formulation of Hadlima™ (biosimilar adalimumab). The Hadlima 50mg/ml formulation was FDA approved in July 2019. Hadlima is expected to be launched on or after 1 July 2023, in accordance with its settlement with AbbVie announced in April 2018.
In its earnings call on 4 August 2022, Coherus announced that it is developing a high concentration adalimumab formulation, which it intends to market following launch of its 50mg/ml citrate-free Yusimry™ formulation in July 2023. Coherus also shared its plans to capture “at least 10%” of the Humira® market in its first year of sales, which is capped by its current manufacturing capacity, although Coherus says it “has the potential to triple that capacity”.
The Court of Appeals for the Seventh Circuit has agreed with the District Court, finding that AbbVie holding 132 US patents relating to Humira®, and settling litigation regarding the same, was not anti-competitive. The decision rejected the appeal filed by welfare benefit payors. The Court commented that there is no cap on the number of patents any one person can hold pertaining to a single subject, that every patent is presumed to be valid, that the appellants have not proved that AbbVie was using invalid patents to protect its monopoly, and that the settlements did not amount to cartel conduct.
A third revocation proceeding was commenced by Samsung Bioepis against a Fresenius Kabi adalimumab 50 mg/mL formulation patent AU2020204269 (‘269). The ‘269 patent covers a specific formulation of adalimumab with a specific buffer, sugar, surfactant and pH. These proceedings were commenced a day after the patent was granted (28 July 2022), following Samsung withdrawing its pre-grant opposition on 27 July (which it filed in December 2020).
Samsung commenced a revocation proceeding in June 2022 against a second, related 50 mg/mL adalimumab formulation patent. In 2019, Samsung also sought revocation of a first Fresenius adalimumab formulation patent, which resulted in Fresenius surrendering the patent in November 2019, the proceedings being dismissed by consent, and a costs order against Fresenius being made against Fresenius.
Celltrion Healthcare has reportedly filed an IND application to the FDA for a phase III clinical trial to demonstrate the interchangeability of its Yuflyma® (adalimumab) biosimilar and AbbVie’s Humira®. The trial will involve 366 patients with plaque psoriasis. Following Celltrion’s aBLA filing in late 2020 and its settlement with AbbVie in Q1 of 2021, Celltrion plans to launch in the US on 1 July 2023.
Sandoz announced that the FDA has accepted its sBLA for a high-concentration citrate-free formulation (100mg/mL) of Hyrimoz® (biosimilar adalimumab). The 50mg/mL formulation of Hyrimoz® was approved by the FDA in 2018 for the treatment of rheumatoid arthritis, juvenile idiopathic arthitis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis and plaque psoriasis.
Alvotech announced that it has initiated a pharmacokinetic study for AVT03 (denosumab, biosimilar to Prolia®/Xgeva®). The study will assess the pharmacokinetics, safety and tolerability of AVT03 compared to Prolia® in healthy adult male subjects.
Alvotech’s portfolio also includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar candidate to Stelara®) for which Alvotech recently announced positive topline results; AVT04 (aflibercept/biosimilar candidate to Eylea®), golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.
Hikma Pharmaceuticals announced that it has entered into a commercialisation agreement with Celltrion in relation to Celltrion’s YuflymaTM (biosimilar citrate-free adalimumab). Under the agreement, Hikma will gain exclusive commercialisation rights to YuflymaTM in all of its Middle East and North Africa (MENA) markets. Hikma has launched a number of Celltrion biosimilars: Truxima® (rituximab), Remsima® (infliximab) and Herzuma® (trastuzumab), with the launch of Remsima® SC (subcutaneous infliximab) in progress.
At the PBAC meetings 6 – 8 July, Australia’s PBAC considered a number of applications for biologic and biosimilar products, including:
Celltrion’s Yuflyma® (biosimilar adalimumab): requesting listing under the same conditions as Humira®
Samsung Bioepis filed a suit against Fresenius Kabi in the AU Federal Court, seeking to revoke AU2020201090 ‘Liquid pharmaceutical composition’ (‘090 patent) which was granted 2 days earlier, on the grounds of novelty, obviousness, lack of utility, lack of best method, lack of clarity and lack of support.
The ‘090 patent is related to Fresenius Kabi’s AU 2015263246 (‘246 patent), which Samsung sought to revoke in 2019. The proceedings were discontinued in early 2020 after Fresenius Kabi surrendered the patent, with Fresenius ordered to pay Samsung’s costs.
The recently granted ‘090 patent, like the earlier granted ‘246 patent, relates to a specific composition of adalimumab, including a histidine buffer, specified sugar and polysorbate.
There is a third granted family member (AU2018222887), which Samsung has not sought to revoke to date, nor has Fresenius asserted it against Samsung.
Sandoz announced that the EMA has accepted its application for high concentration (100mg/mL) citrate-free product Hyrimoz® (biosimilar adalimumab). Sandoz’s application seeks approval for all AbbVie Humira® indications.
Alvotech announced the launch of Hukyndra® (citrate-free 100mg/ml biosimilar adalimumab) in Europe by its partner STADA. The initial launch regions include France, Germany, Finland, and Sweden, with further launches scheduled “over the coming months”. Whilst Hukyndra® is the fifth biosimilar to be marketed by STADA, it is the first arising from its partnership with Alvotech which covers seven biosimilar products.
The Kennedy Institute (Oxford University) published the results of Ph IIb trials of adalimumab in Dupuytren’s disease. The researchers reported no related serious adverse events, and that the treatment was effective. Although the half-life of adalimumab is two or three weeks, researchers saw continued effects nine months after the last injection.
Korea Biomedical Review reported that Celltrion has a licence from AbbVie enabling the launch of Yuflyma® (Celltrion’s biosimilar adalimumab) in the US from July 2023. Celltrion expects to receive approval for Yuflyma® this year. Celltrion previously announced in February 2021 that it had completed patent settlements in the US and was approaching settlements in Europe.
Amgen released its Q1 2022 financial results, reporting a 6% increase in YoY revenues. Amgen reported a 12% increase in Prolia® (denosumab) sales, a 7% decrease in Enbrel® (etanercept) sales, a 2% increase in Amgevita™ (biosimilar adalimumab) sales and a 40% decrease in Kanjinti® (biosimilar trastuzumab) sales.
Celltrion announced the launch of Yuflyma® (high-concentration, low-volume, citrate-free and latex-free biosimilar adalimumab) in Canada. Yuflyma® is approved in Canada for ten indications: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, adult ulcerative colitis, hidradenitis suppurativa, plaque psoriasis, adult uveitis, and paediatric uveitis.
Alvotech announced that it has resolved its patent disputes with AbbVie in Europe and selected markets elsewhere relating to Alvotech’s citrate free, high concentration adalimumab (AVT02, biosimilar to Humira®). This follows the resolution of the US litigation between AbbVie and Alvotech last month and paves the way for Stada to commercialise adalimumab in Europe under the Hukyndra® brand name. AbbVie has granted Alvotech a non-exclusive royalty bearing license to AbbVie’s Humira® patents in Europe and selected markets elsewhere.
Australia’s TGA approved Celltrion’s Yuflyma® (biosimilar to AbbVie’s Humira® adalimumab) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, enthesitis-related arthritis, psoriatic arthritis, ankylosing spondylitis. Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa and uveitis.
Alvotech announced that it has settled all pending US disputes with AbbVie, including the ITC case brought by AbbVie in December 2021. Under the settlement Alvotech will receive non-exclusive rights to market AVT02 (high-concentration, citrate-free biosimilar adalimumab) in the United States from 1 July 2023. This date is the same US license date AbbVie granted to Coherus and Boehringer Ingelheim in their respective settlements with AbbVie, which follows Amgen’s US license date of 31 Jan 23 and Samsung’s 30 June 2023. Alvotech is the only known company that has both developed a high-concentration biosimilar adalimumab and conducted switching studies to enable the launch of what is expected to be the first high concentration interchangeable biosimilar adalimumab in the US. Teva is Alvotech’s strategic partner for the US commercialisation of AVT02. AVT02 is already approved in Europe, Canada and the UK.
Shanghai Junshi Biosciences announced that China’s NMPA has approved its biosimilar adalimumab product (50mg/ml) for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis. The product was jointly developed by Shanghai Junshi Biosciences and Jiangsu T-mab BioPharma (T-mab Bio), a subsidiary of Mabwell (Shanghai) Bioscience Co (Mabwell Bio).
Celltrion launched Yuflyma® (high concentration citrate-free biosimilar adalimumab) in Korea.
The Korea Herald reported that Samsung Bioepis has secured a total of 10 biosimilar products on its 10th year anniversary. Six biosimilars have been approved globally: infliximab, etanercept, adalimumab, trastuzumab, bevacizumab and ranibizumab. Eculizumab has recently completed its Ph III clinical trial, and three other biosimilar candidates are under Ph III trials.
Alvotech announced that the FDA has accepted the BLA including data supporting interchangeability for AVT02, Alvotech’s high-concentration (100mg/ml) biosimilar adalimumab. The Biosimilar User Fee Act goal date for FDA decision is December 2022.
Pfizer announced that the FDA has accepted its sBLA seeking interchangeability for Abrilada™ (biosimilar adalimumab). The Biosimilar User Fee Act goal date for FDA decision is Q4 2022.
Vizient announced that remdesivir has replaced Humira® (adalimumab) as the most expensive drug by total member spend in its Winter 2022 Market Outlook. Pembrolizumab, ustekinumab, ocrelizumab, denosumab, infliximab, nivolumab and tocilizumab also featured in the top 10 most expensive drugs by member spend.
Alvotech and JAMP Pharma announced that Health Canada has approved Simlandi (high-concentration, citrate-free biosimilar adalimumab).
Samsung Bioepis and Organon announced that the FDA has accepted for review the supplemental Biologics License Application for a citrate-free, high-concentration formulation of SB5 (biosimilar adalimumab). Organon expects to launch this product in the US on or after 1 July 2023, in accordance with a licensing agreement with AbbVie.
Health Canada approved Celltrion’s Yuflyma® (100mg/mL biosimilar adalimumab) for all indications as Humira®.
Prestige BioPharma announced that its Ph I study of PBP1502 (proposed adalimumab biosimilar) has been registered with the US National Institute of Health. Prestige disclosed that it plans to file marketing authorisation applications with the EMA and FDA in 2023.
Alvotech and Oaktree Acquisition Corp. II announced that they have entered into a merger agreement for the creation of a publicly-traded global biopharmaceutical company. Alvotech is led by a team of highly experienced biopharma leaders, including Mark Levick as CEO, Anil Okay as CCO, and Philip Caramanica as Chief IP Counsel and Deputy General Counsel. The merger is expected to deliver gross proceeds to Alvotech in excess of USD$450 million. Alvotech currently has seven products in its pipeline, including a biosimilar candidate to Humira® (adalimumab), Stelara® (ustekinumab), Eylea® (aflibercept), Prolia®/Xgeva® (denosumab) and Simponi®/Simponi ARIA® (golimumab).
Mochida Pharmaceutical and Ayumi Pharmaceutical announced the launch of high-dose 100mg/mL Adalimumab BS MA (adalimumab biosimilar) in Japan.
Pharmac announced that it will transfer Principal Supply status from Humira® (adalimumab) to Amgevita® (biosimilar adalimumab) from 01 March 2022.
AU’s PBAC published the outcomes from its July 2021 meeting. PBAC recommended listing:
- Pfizer’s Abrilada® (50mg/mL adalimumab biosimilar) in 20mg/0.4mL syringe, 40mg/0.8mL syringe and 40mg/0.8mL pen for all indications as Humira®.
- Janssen’s Darzalex SC® (daratumumab) for all indications for which the intravenous form of daratumumab is currently listed.
- Pfizer’s Enbrel® (etanercept) in 50mg/1mL single use dose-dispenser cartridges under the same conditions as existing listings for etanercept.
- BMS’ Opdivo® (nivolumab) for the treatment of patients with advanced or metastatic oesophageal squamous cell carcinoma who have disease progression following treatment with a fluoropyrimidine and platinum (FP)-based chemotherapy regimen.
Coherus BioSciences reported its Q3 2021 financial results. Coherus announced that FDA review of CHS-201 (proposed adalimumab biosimilar) is advancing towards the target action date in December 2021. Coherus also disclosed that the FDA has accepted the BLA for its proposed toripalimab biosimilar for advanced nasopharyngeal carcinoma, with a target action date of April 2022.
Pfizer released its Q3 2021 results, reporting a 34% increase operationally in biosimilars. Pfizer announced that it plans to launch citrate-free Abrilada® (biosimilar adalimumab) in the US as early as 1 July 2023 in accordance with its agreement with AbbVie. Pfizer disclosed that it plans to seek interchangeable status for Abrilada® in December 2021.
Boehringer Ingelheim announced that FDA has approved Cyltezo® (biosimilar adalimumab) as the first biosimilar designated as interchangeable with Humira® (adalimumab). Cyltezo® is a 50 mg/mL “citrate free” (ie acetate buffered) product, and the “interchangeable” designation will be limited to only some of the Humira® products, unless FDA responds favourably to the citizen petition lodged by Boehringer Ingelheim in December 2020 requesting FDA to interpret the term “strength” in legislation in section 351(k) of the Public Health Service Act (42 U.S.C. 262(k) in a manner which would extend BI’s interchangeability designation to all formulations delivering the same amount of active (irrespective of concentration). The FDA stated in a May 2021 interim response that it has been unable to made a decision on the CP to date “because it raises complex issues requiring extensive review and analysis by Agency officials”.
The Australian reported that Australian pharmacists have raised concerns over proforma letters provided by AbbVie to prescribing doctors (specialist rheumatologists and gastroenterologists) and public hospital clinics instructing chemists to only dispense Humira® branded adalimumab rather than biosimilar adalimumab.
The US District Court for the Northern District of Illinois dismissed the Humira® trade secrets lawsuit brought by AbbVie against Alvotech for lack of jurisdiction.
AbbVie, Eisai Co and EA Pharma announced Humira® (adalimumab) has received additional approvals in Japan for its high-dose regimen in adults with ulcerative colitis and in a new regimen in paediatric patients.
Alvotech announced that the EU’s CHMP has adopted a positive opinion recommending the approval of AVT02 (proposed adalimumab biosimilar).
Alvotech announced positive top-line results from its switching study between AVT02 (proposed adalimumab biosimilar) and Humira®. Alvotech reported that no significant differences were observed in clinical efficacy, safety or immunogenicity between the switching cohort and the reference cohort.
The US District Court for the Northern District of Illinois refused to dismiss AbbVie’s Humira® (adalimumab) infringement suit against Alvotech hf. The court found that AbbVie is not required to sue the US based subsidiary listed on the aBLA form, but could sue Icelandic company Alvotech hf.
NZ’s Pharmac announced that it is considering awarding Principal Supply to Amgevita® (biosimilar adalimumab). Pharmac is seeking feedback on the proposed changes to the funding arrangements.
Progenity released its Q2 2021 financial results. Progenity disclosed that it has recently produced a GMP drug substance batch for its adalimumab oral biotherapeutics delivery system (PGN-0B1).
A new study published in the The Lancet reported that the safety and efficacy of Boehringer Ingelheim’s BI695501 (adalimumab biosimilar) in patients with Crohn’s disease is similar to reference adalimumab.
Coherus Biosciences released its Q2 2021 financial results. Coherus announced that its partner, Junshi Biosciences plans to submit the BLA for toripalimab for a number of indications later this quarter. Coherus also disclosed that it anticipates a mid-2022 target action date for its BLA for biosimilar ranibizumab, and confirmed it plans to launch its biosimilar adalimumab on or after 1 July 2023.
AbbVie released its Q2 2021 financial results, reporting US Humira® (adalimumab) net revenues increased 7.1%, but decreased internationally 12.6% on an operational basis. AbbVie attributed this decrease to biosimilar competition.
A new study published in Rheumatology reported that the safety and efficacy of Celltrion’s CT-P17 (biosimilar adalimumab) were comparable after one year of treatment, including for patients who switched from reference adalimumab after 24 weeks.
The UK’s NICE finalised its guidance on the treatment of moderate rheumatoid arthritis, recommending the use of adalimumab, etanercept, infliximab and abatacept for patients with moderate rheumatoid arthritis which is inadequately controlled on conventional therapies.
Boditech Med announced it has obtained export approval for AFIAS Adalimumab, a diagnostic kit which measures adalimumab levels in blood. The test is able to return a result within 10 minutes using whole blood on-site.
Alvotech announced it has reached the primary completion date in its switching study for AVT02 (proposed adalimumab biosimilar). Alvotech hopes to list AVT02 as an interchangeable adalimumab biosimilar in the US, which would allow for pharmacy substitution.
The UK’s NICE published final draft guidance recommending adalimumab, etanercept and infliximab for the treatment of moderate rheumatoid arthritis on the NHS. Previously, biologics had been recommended only for severe rheumatoid arthritis.
The Korea Herald has reported that Celltrion will launch Yuflyma® in the EU in June. Citing ‘industry sources’ and a Celltrion official, the article discloses that Celltrion will initially launch Yuflyma® in six EU countries including Spain, before launching in an additional 7 EU countries in Q3 2021, and 3 more in Q4 2021.
AbbVie announced it will present new data from a number of studies on its immunology products including Rinvoq® (upadacitinib), Skyrizi® (risankizumab) and Humira® (adalimumab) at the EULAR 2021 Virtual Congress of Rheumatology.
The US House of Representatives Committee on Oversight and Reform published a Drug Pricing Investigation Staff Report which was scathing regarding AbbVie’s conduct regarding the sale of its blockbuster drugs Humira® (adalimumab) and Imbruvica® (ibrutinib) in pursuing ‘a variety of tactics to increase drug sales while raising prices for Americans, including exploiting the patent system to extend its market monopoly, abusing orphan drug protections to further block competition, and engaging in anti-competitive pricing practices.’.
Alphapharm received approval for Hulio® (biosimilar adalimumab) in Australia. Hulio® was approved in a 20mg/0.4mL solution for pre-filled syringe, 40mg/0.8mL solution for pre-filled syringe, and 40mg/0.8mL solution for pre-filled pen. Viatris launched Hulio® in Canada and Japan in February this year.
Alvotech filed a federal lawsuit against AbbVie in the US District Court of the Eastern District of Virginia, seeking to clear patent barriers relating to proposed biosimilar adalimumab, AVT02. Alvotech alleges that AbbVie has sought to protect its product monopoly by ‘overwhelming’ Alvotech with 60+ patent claims with questionable validity. Specifically, Alvotech alleges that AbbVie has acted improperly by:
- ‘patenting purported inventions that it does not use in the production of Humira®
- seeking multiple patents on the same invention but as part of different patent families in a manner designed to cause confusion;
- obtaining patents through inequitable conduct;
- by seeking patents that cover Humira® already in the prior art; and
- obtaining patents on purported inventions that AbbVie did not invent.‘
AbbVie’s Humira® still holds a monopoly in the US, despite biosimilars being available in the EU, Japan, Canada and Australia.
The Government of Alberta announced it has expanded its biosimilars switching program to include adalimumab for all originator indications except pediatric juvenial idiopathic arthritis. All adult patients on Humira® will be switched to Amgevita®, Hadlima®, Hulio®, Hyrimoz® or Idacio® by 01 May 2022. This follows extensions made to biosimilar switching programs by British Columbia and New Brunswick last month.
Amgen launched Amgevita® (biosimilar adalimumab) in Canada. Amgevita® is available in 50mg/mL PFS and pen presentations and is citrate-free. Amgevita® will be reimbursed on the public drug plans in BC, Alberta, Ontario, Quebec, New Brunswick and Newfoundland.
Merck reported the vision, focus and business model for its new standalone company, Organon. Merck disclosed that Organon with have a direct sales presence in 58 markets, with key growth drivers in Organon’s biosimilars portfolio expected to be Renflexis® (biosimilar infliximab), Aybintio® (biosimilar bevacizumab) and Hadlima® (biosimilar adalimumab).
A new study sponsored by UCB Biopharma SPRL indicates that bimekizumab is noninferior and superior to adalimumab at 16 weeks in the treatment of plaque psoriasis.
Samsung Bioepis released its Q1 2021 financial results. Global sales for Benepali® (biosimilar etanercept), Flixabi® (biosimilar infliximab) and Imraldi® (biosimilar adalimumab) increased 3.9% quarter-on-quarter, with Benepali® accounting for the largest share of those sales.
Boehringer Ingelheim announced results from a Ph III switching study of Cyltezo® (biosimilar adalimumab) with Humira® produced similar clinical outcomes in terms of pharmacokinetics, efficacy, immunogenicity and safety.
British Columbia expanded its biosimilars switching program to include adalimumab, and expanded coverage of etanercept. BC announced that almost 6,000 patients currently treated with Humira® will be switched to either Amgevita® (Amgen), Hadlima® (Merck/Samsung), Hulio® (Mylan), Hyrimoz® (Sandoz) or Idacio® (Fresenius Kabi) over a 6 month period. New and existing plaque psoriasis patients currently being treated by Enbrel® will also be transitioned to Brenzys® (Samsung Bioepis/Merck) or Erelzi® (Sandoz) over the same period.
A new AbbVie study published in the NEJM reports a 30mg dose of upadacitinib is superior to adalimumab in DMARD-refractory psoriatic arthritis (PsA). The percentage of patients with PsA who achieved an ACR20 response at week 12 was 78.5% of patients treated with 30 mg upadacitinib, compared to 65% of patients treated with adalimumab.
Alvotech has disputed AbbVie’s claim filed in the Northern District of Illinois last week relating to AbbVie’s allegations of wrongdoing in the development of Alvotech’s biosimilar adalimumab product. Alvotech notes “AbbVie waited over three years from the purported date of the alleged wrongdoing to file its case, doing so after the ex-AbbVie employee had already left Alvotech and without naming the ex-AbbVie employee as a defendant”, suggesting that these latest accusations may be part of AbbVie’s broader strategy to delay biosimilar competition.
A number of changes have been made to the PBS listings of adalimumab. From 1 April:
- The Amgen, Merck/Samsung, Sandoz and Fresenius 50mg/ml products will be PBS listed and A flagged against the 50mg/ml Humira formulations for all approved indications; and
- Humira 100mg/ml 20mg and 40mg products will be listed and A flagged against the 50mg/ml Humira formulations, and the 50mg/ml Humira product will be phased out over 12 months but cannot be prescribed after 1 April (ie the pharmacies will honour scripts written prior to 1 April).
- Humira 100mg/ml 80mg syringe and pen products will be PBS listed but will not be A flagged as they are not considered equivalent to the “original” Humira formulation/product.
Korea Biomedical Review reported that LG Chem has received approval from Japan’s Health Ministry for its biosimilar adalimumab. The product will be commercialised by Mochida Pharmaceuticals.
Korea Biomedical Review reported that Samsung Bioepis has entered an agreement with Yuhan Corp for the commercialisation of Adalloce™ (biosimilar adalimumab) in South Korea. Adalloce™ is marketed in Europe as Imraldi®.
The EMA published the EPAR for Celltrion’s Yuflyma®. The EPAR revealed that Celltrion’s product is citrate-free, but is not buffer-free, with other ingredients including ‘acetic acid, sodium acetate trihydrate, glycine, polysorbate 80 and water for injections’.
Cipla and Alvotech announced that they have expanded their partnership for the marketing and distribution of four biosimilar medicines in Australia and New Zealand. The agreement includes biosimilar aflibercept, ustekinumab, denosumab and golimumab candidates. This agreement is in addition to the previous agreement between Alvotech and Cipla for the commercialisation of AVT02 (biosimilar adalimumab candidate).
Coherus released its Q420 and Full Year 2020 financial results. Coherus reported it has captured 21% of the pegfilgrastim market and nearly 50% of the pre-filled syringe segment in the US. Additionally, Coherus announced it plans to file its BLA for its ranibizumab biosimilar mid-year 2021. Coherus also confirmed that it plans to launch its adalimumab biosimilar in the US on or after July 1, 2023.
In its Q4 2020 investor presentation, Fresenius Kabi announced it will launch its biosimilar adalimumab in Australia in Q2 2021 and in Brazil in Q3 2021. Additionally, Fresenius Kabi announced it will launch its biosimilar pegfilgrastim in the US and the EU in Q3/4 2021. Fresenius Kabi’s biosimilar tocilizumab candidate is planned for launch in the US and the EU in 2023. An undisclosed autoimmune biosimilar is planned for a 2024 launch, and an oncology biosimilar in 2025.
Viatris announced it has launched Hulio® (biosimilar adalimumab) in Canada. Hulio® is available in a 50mg/ml formulation (40mg/0.8mL) and is approved for all adalimumab indications.
Fresenius Kabi announced it has launched Idacio® (biosimilar adalimumab) in Canada. Idacio® is available in 50mg/ml formulation (40mg/0.8mL syringe, vial and pen presentations) and is approved for all Humira® indications.
Sandoz announced that it has launched Hyrimoz®, its 50mg/mL biosimilar adalimumab in Canada. Hyrimoz® was approved by Health Canada in November 2020 with a full label. It was also previously launched in Europe in 2018.
Coherus Biosciences announced the FDA has accepted the BLA for its biosimilar adalimumab candidate (CHS-1420). Coherus also announced that it plans to launch its product in the US on or after 01 July 2023. Coherus had previously disclosed that its license with AbbVie would commence in the US in December 2023.
Fujifilm Kyowa Kirin Biologics and Mylan announced the launch of Hulio® in Japan. Hulio® is available in a 40mg/0.8mL syringe and pen presentation (indicated for rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, ankylosing spondylitis, Entero-Behcet’s Disease and Crohn’s Disease), and a 20mg/0.4mL syringe (indicated for juvenile idiopathic arthritis). This is the first adalimumab biosimilar to be launched in Japan.
Celltrion announced it received EC marketing authorisation for Yuflyma® (biosimilar adalimumab) across all indications. This is the first approval of a high concentration, low-volume biosimilar adalimumab. The EPAR is yet to be published by EMA.
In an interview with the Centre for Biosimilars the head of Celltrion’s Medical and Marketing Division, HoUng Kim PhD, discussed its high concentration, citrate-free adalimumab biosimilar. Kim announced that Celltrion has completed patent settlements in the US and is approaching settlements in Europe. Kim also revealed that the application for Celltrion’s US biosimilar adalimumab product was filed in November 2020.
Health care performance improvement company Vizient releases its Winter 2021 Pharmacy Market Outlook. Vizient projected that the greatest price increases to members would occur in Humira® (adalimumab), with a 7.5% price increase predicted over the next 18 months. Adalimumab also topped the list of greatest total spend by product among Vizient members, followed by pembrolizumab, rituximab, infliximab, ustekinumab, nivolumab and denosumab. New figures also showed trastuzumab biosimilars have captured a significant market share, contributing to 39% of cost to members in September 2020.
Celltrion receives a positive opinion from the EU’s CHMP for its proposed 100mg/mL adalimumab biosimilar Yuflyma® for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis, paediatric plaque psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis and uveitis. If approved, this will be the first registered high concentration, citrate-free adalimumab biosimilar anywhere in the world.
Shanghai Henlius Biotech announces its adalimumab biosimilar HLX03 has been approved by China’s NMPA for rheumatoid arthritis, ankylosing spondylitis and plaque psoriasis.
Novartis released its annual report ‘Meet Novartis Management 2020‘. In the report, Novartis announced that GP2411 (biosimilar denosumab candidate) has commenced Ph III trials. Novartis has also indicated it has planned launches for biosimilar adalimumab and natalizumab in 2021-2023 and denosumab in 2024-2026.
BGP Pharma receives a NOC from Health Canada for Hulio® (biosimilar adalimumab).
Alvotech announces the FDA and EMA have accepted its regulatory submissions for AVT02 (proposed adalimumab biosimilar). Approval is expected in the US in September 2021 and Q4 2021 in the EU.
Amgen receives three Notices of Compliance (NOC) from Health Canada relating to Amgevita® (50mg/mL biosimilar adalimumab).
Celltrion announces the results of Ph III studies of CT-P17 (proposed adalimumab biosimilar) demonstrate comparable efficacy and safety against reference adalimumab in rheumatoid arthritis.
Fresenius Kabi receives a Notice of Compliance relating to its biosimilar adalimumab (50mg/mL), Idacio®.
Two amicus briefs were filed in the 7th Circuit Court of Appeals in support of the plaintiffs in the Humira® (adalimumab) antitrust legislation UFCW Local 1500 Welfare Fund v AbbVie, Inc. The US Public Interest Research Group jointly filed its brief with Consumer Action, arguing that AbbVie’s conduct was anticompetitive, and that the District Court’s decision should be overturned. In its brief, the Open Markets Institute argued that the District Court should have evaluated AbbVie’s patent applications and lawsuits as a series of sham filings.
The University of Oxford announces it has commenced Ph II trials of adalimumab as a treatment for patients with COVID-19. The trial will enrol up to 750 patients from community care settings throughout the UK and is funded by the COVID-19 Therapeutics Accelerator, an initiative set up by Wellcome and Mastercard. The trial will assess Hyrimoz® (biosimilar adalimumab), developed by Sandoz.
Innovent Biologics announces China’s NMPA has approved Sulinno® for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis.
Cadila Pharmaceuticals launches Cadalimab® (biosimilar adalimumab) in India. Cadalimab® is available in 40mg/0.8mL injection and is indicated for rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis and psoriasis. This is the fourth biosimilar launch in India by Cadila within 2 months following Bevaro® (biosimilar bevacizumab), Ritucad® (biosimilar rituximab) and NuPTH® (biosimilar teriparatide).
PBS publishes the outcomes of the July 2020 meeting including a positive recommendation for Merck’s application to broaden out the PBS reimbursed indications for its Hadlima® (biosimilar adalimumab). Merck’s Hadlima® was first granted PBS listing in 2018 for rheumatoid arthritis only. The expanded recommendation follows Sandoz’s positive recommendation for Hyrimoz® earlier this year, which included the same indications as Humira®.
Healio reports a new article published in the Annals of the Rheumatic Diseases showed that ixekizumab demonstrated significantly greater joint and skin improvement than adalimumab among patients with psoriatic arthritis (PsA). The 52 week SPIRIT trial assessed 566 adults with PsA who had not yet been treated with a biological disease-modifying anti-rheumatic drugs.
Celltrion releases its Q2 FY20 earnings report. Celltrion reported that it is “preparing” its US approval application for CT-P17 (biosimilar adalimumab candidate), following the filing of its application in the EU in March this year.
The Centre for Biosimilars reports a study presented at the American Academy of Dermatology’s Virtual Meeting Experience 2020 demonstrates the safety, efficacy and immunogenicity of Boehringer Ingelheim’s Cyltezo® (biosimilar adalimumab) is comparable to AbbVie’s Humira®.
Spherix reports that the EU market for AbbVie’s Humira® has been negatively impacted by gastroenterologists increasingly prescribing alternative mechanism of action agents, including Stelara® (ustekinumab) and Entyvio® (vedolizumab) for ulcerative colitis (UC) and Crohn’s disease (CD) and the increased prescription of adalimumab biosimilars. These increases have come at a cost to AbbVie, with use of Humira® in UC and CD decreasing in the EU.
FDA approves Hulio®
Mylan announces FDA approval of Hulio® (biosimilar adalimumab) for PFS and auto-injector presentations.
Fujifilm Kyowa Kirin Biologics announces manufacturing and marketing approval in Japan for FKB237 (adalimumab biosimilar). This product was developed in partnership with Mylan and has been marketed as Hulio® in 20 countries across Europe.
TGA approves Idacio®
Fresenius Kabi receives Australian approval for Idacio® (biosimilar adalimumab) with identical indications as Humira®, in 40mg vial, PFS and pen.
A new study published in BMC Rheumatology reports that Hetero’s biosimilar adalimumab Mabura® was effective and well tolerated in comparison to Humira® in patients with active rheumatoid arthritis.
The Big Molecule Watch reports that a US District Court Judge ruled AbbVie’s conduct in relation to its blockbuster Humira® (adalimumab), while preventing competitors from reaching the market in the US, was not illegal. The action was filed against AbbVie by a number of parties including the City of Baltimore and a pension for Police Officers, and alleges that by amassing a ‘patent thicket’ and settling litigation with competitors which prevented them launching in the US, AbbVie had engaged in conduct which breached federal and state antitrust laws.
Fresenius Kabi announces it has signed an agreement with Medac to cooperate in Germany in the area of treatments for rheumatic illnesses. From 01 June 2020, Medac’s sales representatives will be able to offer Fresenius Kabi’s adalimumab biosimilar Idacio. Medac is already a provider of methotrexate, a product which is often used in combination with adalimumab.
Shanghai Henlius Biotech announces that its adalimumab and trastuzumab products are under New Drug Application review, with the potential to be launched in 2020.
Alvotech releases the results of two studies for AVT02, a proposed adalimumab biosimilar, announcing both studies met their primary endpoints. Alvotech announced that the Ph I clinical study demonstrated the PK similarity of AVT02 to the reference product Humira®, while the Ph III study demonstrated equivalent efficacy compared to Humira® in patients with moderate-to-severe chronic plaque psoriasis.
Results of the Novartis’ EXCEED study comparing adalimumab and secukinumab for the treatment of PSA (psoriatic arthritis) were released. Researchers reported no statistically significant superiority between secukinumab and adalimumab as first-line treatment of psoriatic arthritis, but secukinumab was associated with a higher treatment retention rate than adalimumab.
AbbVie released its Q1 2020 financial results, reporting a 13.7% increase in US sales of Humira® from Q1 2019. In global markets, Humira® sales were down 14.9%, a decline that was attributed to biosimilar competition.
Alvotech and DKSH announce an exclusive license partnership for the commercialisation of AVT02 (adalimumab candidate) in 36 emerging countries in South-East Asia. Under the agreement, Alvotech will be responsible for development and supply and DKSH will be responsible for registration and commercialisation.
Hisun Pharmaceuticals completes Phase III trials of HS016 (adalimumab). Researchers concluded that HS016 was similar to adalimumab in terms efficacy and safety in the treatment of ankylosing spondylitis.
Celltrion submits its application for CT-P17 (adalimumab) to the EMA. If approved, CT-P17 will be the first high-concentration adalimumab available.
AbbVie outlines defence strategy for Humira® (adalimumab) competition in the US market. CEO Gonzalez stated that AbbVie’s strategy will be based on the strategy already employed in Europe and other markets, while also admitting that global competition was much more aggressive than had been predicted.
AbbVie management acknowledge losses will be felt when biosimilar adalimumab products launch in the US market in 2023. Drawing from an international profit erosion of 45-48% for Humira® in 2019, AbbVie’s CEO Gonzalez warned stakeholders that biosimilar competition in the US would further impact profits. Gonzalez also noted that the erosion rate in the US would not be directly comparable to European markets as it would be heavily impacted by negotiations with managed care and pharmacy benefit managers.
We previously reported that Fresenius Kabi surrendered its patent AU2015263246 in the patent office in November 2019, which was the subject of a revocation suit commenced by Samsung Bioepis in July 2019. The Court entered orders today dismissing the proceeding by consent, and ordering Fresenius to pay Samsung’s costs.
Mundipharma announces commercialisation agreement with Samsung. The agreement grants Mundipharma exclusive commercialisation rights to Samsung’s adalimumab candidate in Taiwan and Hong Kong.
Bio-Thera launches adalimumab biosimilar, Qletli® in China following Nov 2019 approval.
US Court of Appeals affirms US PTAB’s earlier decision, which invalidated three AbbVie patents (8,889,135, 9,017,680 and 9,073,987) as obvious. The initial challenges to these patents were brought by Coherus and Boehringer Ingelheim, who have since settled with AbbVie, leaving the appeal to be defended by the USPTO.
Pfizer receives positive CHMP opinion for its biosimilar adalimumab product.
Boehringer Ingelheim has released the results of its Ph III trials of its biosimilar adalimumab, announcing the product demonstrated non-inferior efficacy and similar safety profile to the originator.
Coherus and Amgen settle suit over adalimumab. Notice of the agreement has been approved by a US Federal Court, however no further details about the settlement have been published. This dispute arose when Amgen launched Amgevita® in Europe in 2018 (manufactured in the US), with Coherus alleging the product infringed 4 of its own patents.
FDA approves Pfizer’s adalimumab biosimilar Abrilada®. This product will not be launched until November 2023, under the terms of Pfizer’s agreement with AbbVie entered into in November 2018.
Bio-Thera announces China’s National Medicinal Products Administration has approved its biosimilar adalimumab, Qletli® for the treatment of rheumatoid arthritis, ankylosing spondylitis and plaque psoriasis.
Biogen and Samsung Bioepis announce partnership for the commercialisation of biosimilar ranibizumab and aflibercept for major markets world side including the US, Canada, Europe, Japan and Australia. Biogen has also acquired exclusive commercialisation rights for its anti-TNF portfolio, including BENEPALI® (etanercept), FLIXABI® (infliximab) and IMRALDI® (adalimumab), in China. Under the agreement, Biogen will make one $100 million upfront payment, with up to $210 million payable at additional development, regulatory and sales-based milestones.
AbbVie releases Third-Quarter results, showing an overall decrease in Humira® revenues of 3.7% due to biosimilar competition. While Humira® revenues continued to increase in the US by 9.6%, internationally revenues decreased by 33.5%.
The Institute for Clinical and Economic Review releases its report on Unsupported Price Increases, highlighting AbbVie’s Humira® as one of the products with price increases which are unsupported by new clinical evidence.
NHS announces saving of £110 million by using AmAb biosimilars since AbbVie’s Humira® lost patent protection in October 2018.
Results of Phase III trial of proposed adalimumab biosimilar demonstrate therapeutic equivalence in terms of efficacy, safety and immunogenicity. The results, published in the first issue of the Lancet Rheumatology, support Innovent’s bid to launch the first biosimilar adalimumab in China.
Momenta announces it has dropped proposed AmAb biosimilar candidate, M923, citing changes in market opportunity due to patent litigation settlements.
Alvotech and Cipla announce they have entered an exclusive arrangement relating to the commercialisation of AVT02, Alvotech’s biosimilar adalumimab. Alvotech is responsible for development and supply of the product, while Cipla is responsible for registration and commercialisation. AVT02 is in Phase-3 clinical development with an expectation that applications will be filed with EMA and FDA by “early 2020”.
Samsung announces FDA approval of adalimumab biosimilar, Hadlima® for RA, JIA, PSA, Crohn’s, UC, PP and AS. This is Samsung’s third biosimilar anti-TNF Ab approval in the US. It will be marketed by Merck in the US, after 30 June 2023 pursuant to the terms of Samsung’s settlement with AbbVie.
Alvotech announces completion of enrolment in Phase III trials of biosimilar adalimumab AVT02. 407 participants across Europe have enrolled, while Phase I PK trials are ongoing.
ES | EU |
Mylan launches Hulio® in Spain
Mylan launches Hulio® in Spain following EC approval in September 2018.
Sandoz announces results of Hyrimoz® switching studies in patients with moderate-to-severe rheumatoid arthritis, announcing no clinically meaningful differences in safety, efficacy or immunogenicity.
Samsung BioLogics announces Imraldi® dominates 46% share in European adalimumab biosimilar market.
AbbVie announces global settlement with Boehringer Ingelheim. This is the 9th global deal AbbVie has entered into, with BI securing a US market entry date of 1 July 2023, after Amgen (31 Jan 2023) and Samsung Bioepis (30 Jun 2023), and before Mylan (31 Jul 2023), Fresenius Kabi and Sandoz (30 Sept 2023), Momenta Pharmaceuticals and Pfizer (20 Nov 2023), and Coherus BioSciences (15 Dec 2023). The agreement is royalty bearing, however no further details have been released.
EMA approves Idacio®
Fresenius Kabi announces European Commission approval of biosimilar adalimumab, Idacio® for all indications.
The Mayor and City Council of Baltimore files additional class action against AbbVie, alleging that anti-competitive behaviour prevented the introduction of biosimilars and allowed AbbVie to demand ‘supra competitive prices’. Additionally, the complaint alleges that through the agreements reached with AbbVie, Amgen has been awarded a 5 month period with reduced competition as the only biosimilar available from January 2023.
Celltrion announces completion of recruitment for Phase III clinical trials of biosimilar adalimumab.
UFCW Local 1500 Welfare Fund, a grocery union, files class action against AbbVie, Amgen, Samsung Bioepis, Mylan, Sandoz, Fresenius Kabi, Pfizer and Momenta, alleging misconduct and antitrust violations. The union alleges that the hundreds of patents which protect Humira® and settlements reached which the other seven companies have resulted in a monopoly which has prevented any competition. The class action includes persons or entities who have purchased or paid for Humira® since January 1, 2017.
Alvotech commences Phase III trial of 100mg/mL adalimumab biosimilar. 400 participants will be enrolled across 30 sites in Europe in this comparability study.
Sandoz obtains Sandoz Australian approval for biosimilar adalimumab Hyrimoz®. This is the third biosimilar adalimumab approval in Australia.
In ongoing litigation between Boehringer and AbbVie, the court has ordered Boehringer to release its plans for biosimilar adalimumab, Cytelzo®. Cytelzo® has been approved by the FDA but has not yet been launched.
Coherus announces an 8th global deal with AbbVie for the commercialisation of biosimilar AmAb, under which Coherus has global, non-exclusive license rights which are royalty bearing. Coherus’ US rights commence on 15 Dec 2023, just under a month after Momenta’s & Pfizer’s.
The NHS announces negotiations for the supply of adalimumab biosimilars have concluded with Amgen, Biogen, Mylan, Sandoz and AbbVie. This deal is predicted to save the NHS £300M per year.
Pfizer notifies the CHMP it wishes to withdraw its application for Fyzoclad®, biosimilar adalimumab, due to changes in the company’s strategy.
AbbVie announces a 7th global deal for biosimilar adalimumab. A non-exclusive royalty bearing license to Pfizer for AmAb will begin on 20 November 2023 in the US and on approval in the EU (no other dates disclosed). Pfizer’s US launch date is the same as Momenta’s, 10 months after the first licensed biosimilar launch (Amgen).
China’s National Medical Products Administration accepts Innovent’s application for biosimilar adalimumab. The application seeks approval for the treatment of ankylosing spondylitis, rheumatoid arthritis, and psoriasis.
AbbVie announces a 6th global deal for biosimilar AmAb, this time with Momenta. Momenta has obtained a global royalty bearing licence beginning on 20 November 2023 for the US, and in the EU “on approval” (no other dates disclosed). Momenta will be able to launch in the US 10 months after Amgen, with Samsung, Mylan, Fresenius and Sandoz able to launch between June and September of 2023.
FDA approves Sandoz adalimumab biosimilar Hyrimoz® for treatment of rheumatoid arthritis, juvenile idiopathic arthitis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis and plaque psoriasis.
Mylan announces launch of Hulio®, biosimilar adalimumab in Europe.
AbbVie and Fresenius separately announce global deal with Fresenius Kabi under which Fresenius has a US licence from 30 Sept 2023 (the same date as Sandoz), and may sell in EU on approval. The deal is global, and different dates apply for other regions. The Fresenius (and Sandoz) US launch date is 9 months after Amgen’s (31 Jan 2023), 3 months after Samsung Bioepis’ (30 Jun 2023), and 2 months after Mylan’s (31 Jul 2023).
Sandoz, Samsung and Amgen launch their biosimilar adalimumab products (Hyrimoz®, Imraldi® and Amgevita®) pursuant to the terms of their IP licences with AbbVie. Mylan also has EMA approval (but no AbbVie EU IP licence) but has indicated an intention to launch their biosimilar Hulio® on or after 16 October. Similarly Boehringer has no IP licence, but we have no indication of BI’s launch plans for approved Cyltezo®
AbbVie announces global settlement with Sandoz, under which Sandoz receives a royalty-bearing, non-exclusive licence to AbbVie’s Humira® patents from 30 Sep 2023 in the US, and 16 Oct 2018 in EU (and other dates elsewhere). The EU date is the same as AbbVie has given to Amgen and Samsung Bioepis (note – Mylan has no EU license), and the US date is later than those given to Amgen (31 Jan 2023), Samsung Bioepis (30 Jun 2023) and Mylan (31 Jul 2023).
Momenta announces an end to its strategic review, revealing a sole focus to advance a Humira® biosimilar. Momenta announced it will file a BLA with the FDA and is working to find a commercialisation partner for the product.
EMA approves Hulio®
Mylan announces the EU approval of Hulio®, biosimilar adalimumab licensed from Fujifilm in April 2018.
Bio-Thera announces that the CNDA (China National Drug Administration) has accepted its BLA for biosimilar adalimumab BAT1406. This is expected to be Bio-Thera’s first drug approval.
Celltrion announces Phase I and III trials for AmAB biosimilar across 75 sites in 8 European nations, expected to be completed by 2020.
AU’s PBAC has confirmed that Amgen and Samsung’s biosimilar adalimumab (respectively Amgevita and Hadlima) will be “A-flagged”, enabling pharmacy substitution.
Sandoz announces EC approval for Hyrimoz®, biosimilar adalimumab for use in all indications.
Mylan and Fujifilm announce positive response from CHMP for biosimilar adalimumab for use in all indications.
AbbVie announces a global settlement with Mylan under which Mylan acknowledges Humira® AbbVie’s patents are valid, and Mylan receives a royalty-bearing, non-exclusive global license (excluding Europe) from 31 July 2023. This date will not be accelerated by entry of Amgen or Samsung Bioepis.
US Senators Chuck Grassley and Amy Klobuchar urge FTC to investigate ‘pay-for delay’ settlements, in particular AbbVie’s Humira settlements, for anti-competitive behaviour. Of particular concern is investigating whether these settlements are keeping biosimilars out of the hands of patients.
Fresenius reports the results of its Ph III studies for biosimilar adalimumab MSB11022 in moderate-to-severe chronic plaque psoriasis at the European League Against Rheumatism’s Annual European Congress of Rheumatology.
Coherus BioSciences confirms its 2022 target launch date for CHS-1420, biosimilar adalimumab. Commercial partnering options are being considered.
Samsung announces a royalty-bearing, global settlement with AbbVie enabling Samsung to launch its SB5 biosimilar adalimumab in Europe from 16 October 2018 and in the US from 30 June 2023. The EU date is the same as AbbVie gave Amgen’s in its September 2018 global settlement, but the US date is 5 months later than Amgen’s licensed date of 31 Jan 2023. SB5 is registered in EU as Imraldi® and in AU as Hadlima®.
The second biosimilar AmAb, Samsung Bioepis’ Hadlima®, is registered on the ARTG in 2 different dosages.
Sandoz announced the FDA has accepted for review its application under s351(k) for biosimilar adalimumab.
At the JP Morgan conference, Richard Gonzalez, (chairman of the board and CEO of AbbVie) confirms that AbbVie does not expect biosimilar competition for Humira® until 2022.
Glenmark announces the launch of biosimilar adalimumab (developed by Zydus, marketed as Adaly®), in India.
EMA approves BI’s Cyltezo® (adalimumab biosimilar) for the treatment of multiple chronic inflammatory diseases in adults and children.
The first biosimilar adalimumab, Amgen’s Amgevita®, is registered on the ARTG in 3 different dosages.
BI publishes results from switching study showing efficacy and safety maintained in patients who switched from Humira® to biosimilar Cyltezo®.
Coherus publishes phase 3 studies on proposed biosimilar adalimumab, CHS-1420.
Hexal/Parexel publishes results of PK, immunogenicity and safety studies relating to proposed adalimumab biosimilar GP2017.
Amgen and AbbVie settle global patent disputes regarding adalimumab, and Amgen secures a royalty-bearing, non-exclusive license to AbbVie’s Humira® IP. Amgen’s license commences in the US on 31 Jan 2023, in most EU countries on 16 Oct 2018, and “on other dates in various countries in which AbbVie has intellectual property.”
Samsung says it has approval to sell biosimilar adalimumab in South Korea, but will delay launch due to patent expiry.
BI receives positive CHMP opinon on Cyltezo®, biosimilar to adalimumab. Approval is expected in Q4/17.
Sandoz announces at the EADV results from 51 week clinical study confirming that Sandoz’s biosimilar adalimumab matches Humira® in safety and efficacy profile.
PTAB denies institution of Coherus Biosciences’ 4 IPR petitions against AbbVie’s 9,085,619 relating to the Humira® formulation.
Boehringer Ingelheim Pharmaceuticals, Inc. receives FDA approval for Cyltezo® (adalimumab-adbm), a biosimilar to Humira®. This is the first biosimilar from BI to be FDA approved. According to the release:
- Cyltezo® is not yet commercially available due to the active patent litigation between Boehringer Ingelheim and AbbVie.
- EMA is expected to provide an opinion on BI’s EU application in 2017.
Imraldi®, Biogen/Samsung’s adalimumab biosimilar approved in the EU.
AbbVie commences BPCIA proceedings against Boehringer Ingelheim for Humira® (adalimumab) biosimilar in the District Court of Delaware, alleging infringement of 8 patents: (8,926,975; 9,018,361; 9,090,867; 9,096,666; 9,255,143; 9,266,949; 9,272,041; and 9,546,212), a subset of the 74 listed under § 262(l)(3)(C) and § 262(l)(7). Two of the patents in suit overlap with the 10 patents in suit in the earlier Delaware proceedings commenced against Amgen in August 2016 (8,663,945; 8,911,964; 8,916,157; 8,961,973; 8,986,693; 9,096,666; 9,220,781; 9,272,041; 9,359,434; and 9,365,645) which has been set down for hearing on 4 November 2019. AbbVie alleges those 10 patents are a subset of 61 patents in dispute, the remainder of which could be addressed in phase 2 BPCIA litigation.
BI commences interchangeability studies between biosimilar BI695501 and Humira 40mg/0.8ml, with the results expected in second half of 2019.
Imraldi®, Samsung’s adalimumab biosimilar (SB5) receives positive opinion from CHMP in EMA.
Fujifilm announces EC has accepted its MA for biosimilar adalimumab (FKB327) which Fujifilm filed in April 2017. Clinical trials were conducted in RA and commenced in Dec 2014.
EMA approves Amgen’s biosimilar adalimumab Amgevita® with a full indication set. This is the first EU approval for biosimilar adalimumab.
UK High Court hands down decision in Samsung v Abbvie.
CHMP (Committee for Medicinal Products for Human Use) for EMA gives positive opinion for Amgen’s biosimilar adalimumab.
Amgen/Allergan submit EMA application for biosimilar adalimumab.
FDA approves Amgen’s biosimilar to adalimumab, Amjevita™ (adalimumab-atto), 11 months after Amgen’s application was filed.
Samsung announces the EMA has accepted for its review its application for adalimumab biosimilar.
Amgen announces FDA Advisory Committee Meeting to review ABP 501 (biosimilar adalimumab). FDA has set a Biosimilar User Fee target action date of 25 September 2016.
FDA’s Arthritis Advisory Committee reviews data supporting Amgen’s BLA for ABP 501 (biosimilar adalimumab).
Samsung Bioepis files suit in the UK to remove Abbvie patents regarding adalimumab.
Amgen submits BLA under s351(k) pathway for ABP 501 (proposed adalimumab biosimilar).
Product specific reports based on extracts from our BioBlast® database
BioBlast® Editor and Contributing Author
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