BioBlast®

On 22 March 2024, the first case management hearing was held before Justice Nicholas in the Federal Court of Australia, Sydney, in proceedings commenced by Samsung Bioepis for revocation of at least two Janssen patents regarding the use of ustekinumab for the treatment of ulcerative colitis.  Samsung Bioepis informed the Court that it has applied for regulatory approval of its biosimilar referencing Stelara® and is expecting PBS (reimbursement) approval in July/August 2025.   The Court has provisionally scheduled a trial for 18 – 22 November 2024.

On 13 March 2024, Sandoz reported double-digit growth of 15% in its 2023 biosimilar sales.  Sandoz attributed this growth to the launch of Hyrimoz®(biosimilar to AbbVie’s Humira®,adalimumab)  in the US and entering an agreement to commercialise Samsung Bioepis’ SB17 (biosimilar to Janssen Biotech’s Stelara®) in the US, Canada, EEA, Switzerland, and UK.

In March 2024, Sandoz announced completion of its acquisition of Coherus Biosciences’ Cimerli®, biosimilar to Genentech’s Lucentis® (ranibizumab), for US$170M.

Johnson and Johnson (J&J) and Janssen have filed a Motion to Dismiss a class action brought by several US health insurers alleging the companies unlawfully delayed biosimilar competition for Stelara® (ustekinumab) in the US.  J&J/Janssen argue that the alleged facts do not meet the standard of unlawful exclusionary conduct. 

The insurers filed the class action in the US District Court of East Virginia on 7 December 2023, alleging that the companies would lose exclusivity for Stelara® in the US on 25 September 2023 upon expiration of the relevant composition patent, and implemented a scheme to unlawfully prolong patent protection.   

On 29 February 2024, Biocon Biologics Ltd, announced a settlement with J&J and Janssen, under which it can launch its Bmab 1200 (ustekinumab), biosimilar to Janssen’s Stelara®, in the USA from February 2025.  The FDA previously accepted for review Biocon’s Biologics License Application for Bmab 1200. 

The settlement will result in the termination of the pending Inter Partes Review petition filed by Biocon in November 2023 against Janssen’s US method of treatment (severely active ulcerative colitis (UC)) patent 10,961,307 relating to Stelara® (ustekinumab). 

J&J and Janssen recently entered into ustekinumab settlements with Alvotech (launch dates of no later than 21 February 2025 (US), May 2024 (Japan), late July 2024 (EU) and Q1 2024 (Canada)), BioPharma (US launch date of 15 May 2025), Samsung Bioepis (US launch date from 22 February 2025), Celltrion (US launch date of 7 March 2025), Fresenius Kabi and Formycon (US launch date no later than 15 April 2025), and Amgen (US launch date no later than 1 January 2025).  To date, only Amgen has obtained FDA approval for its ustekinumab biosimilar, with its Wezlana® approved in October 2023. 

On 23 February 2024, Samsung Bioepis presented two new study results for ustekinumab SB17 (biosimilar to Janssen’s Stelara®) at the 19th Congress of European Crohn’s and Colitis Organisation (ECCO) in Stockholm, Sweden.  The results demonstrate SB17 is highly similar to Stelara® in structural, physicochemical, and biological attributes.  On 25 February 2024, CHMP provided a positive recommendation for SB17.   

The medicine will be commercialised by Sandoz in the US, Canada, EEA, Switzerland and the UK under an exclusive commercialisation agreement  entered in September 2023.  

On 22 February 2024, EU’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Samsung Bioepis’s Pyzchiva® (ustekinumab biosimilar).  Pyzchiva® is recommended for the treatment of plaque psoriasis, including paediatric plaque psoriasis, psoriatic arthritis, ulcerative colitis and Crohn’s disease in adults.  Pyzchiva® is intended to be supplied as 45 mg and 90 mg solutions for injection and a 130 mg solution for infusion.  

Pyzchiva® will be commercialised by Sandoz pursuant to a deal entered into in September 2023, between Sandoz and Samsung Bioepis for SB17 which covers the US, Canada, EEA, Switzerland and the UK. 

According to the Pharmaceutical Benefits Assessment Committee (PBAC) agenda for March 2024, published on 5 January 2024, the meeting will be jammed with biopharma applications for reimbursement.  The applications for PBS listing additions or amendments that the PBAC will consider at its March 2024 meeting include the following: 

In addition, a number of PBAC recommendations not accepted by applicants are set for review, including relating to AbbVie’s Skyrizi® (risankizumab), and Novartis’s Cosentyx® (secukinumab). 

A paper published in the journal BioDrugs reported the results of a Phase III study conducted in Eastern Europe and the Republic of Korea comparing the efficacy, safety, pharmacokinetics and immunogenicity of Celltrion’s CT-P43 with Janssen’s Stelara® (ustekinumab).  The study, conducted in 509 patients with moderate to severe plaque psoriasis, demonstrated equivalent efficacy and comparable pharmacokinetic, safety and immunogenicity profiles. 

On 5 February 2024, Rani Therapeutics published positive topline results from its phase I clinical trial on RT-111, an oral formulation of CT-P43.   

Carefirst and another Blue Cross/Blue Shield licensee have brought class action proceedings against Johnson & Johnson (J&J) and Janssen alleging that the companies unlawfully delayed the introduction of biosimilar competition for its Stelara® ustekinumab product onto the US market.  The complaint alleges that J&J would lose exclusivity for Stelara® in the US on 25 September 2023 upon expiration of the relevant composition patent, and that J&J delayed biosimilar competition through a series of unlawful acts to unlawfully prolong patent protection for Stelara® well beyond September 2023.

The acts alleged in the Class Action include defrauding the US Patent and Trademark Office into incorrectly issue a patent to the use of ustekinumab to treat ulcerative colitis, acquiring the company Momenta, which held patents to manufacturing methods for ustekinumab, and suing or threatening suit of would-be biosimilar entrants for patent infringement. 

Biocon Biologics filed an Inter Partes Review (IPR) petition against Janssen’s US patent no. 10,961,307 relating to Stelara® (ustekinumab).  Biocon Biologics is challenging all 34 claims of the patent, relating to methods of treating ulcerative colitis with ustekinumab.

On 9 August 2023, the USPTO Patent Trial and Appeal Board terminated Samsung Bioepis’s IPR challenging the ‘307 patent following Samsung and Janssen’s joint motion for termination on the basis that the parties had resolved the dispute.

A Phase III study funded by Celltrion compared the efficacy and safety of its ustekinumab biosimilar CT-P43 to Janssen’s Stelara® (ustekinumab).  The study concluded that CT-P43 was equivalent in efficacy in treating patients with moderate to severe plaque psoriasis, and had comparable pharmacokinetic, safety and immunogenicity profiles to Stelara®. 

In April 2023, Celltrion filed an application in Australia seeking approval of CT-P43 for all Stelara® indications, including plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. 

On 21 November 2023, the Canadian Federal Court of Appeals dismissed Janssen’s appeal from a decision of the Federal Court upholding Canada’s Office of Submission and Intellectual Property (OSIP) refusal of Janssen’s application to list Canadian Patent 3113837 on the PMNOC register for two supplementary new drug submissions relating to Stelara® (ustekinumab).

The Federal Court decision was handed down in July 2023.

Alvotech and its EU partner Stada announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for ustekinumab Uzpruvo (AVT04), biosimilar to Janssen’s Stelara^®.  This is the first positive CHMP opinion for a Stelara^® biosimilar.

The Alvotech and Stada MAA was accepted by the EMA in February 2023.

Under their 2019 strategic partnership for seven biosimilars, Alvotech is primarily responsible for developing and manufacturing AVT04, and Stada holds commercial rights within Europe.  In May 2023 Alvotech announced that it had terminated the Stada agreement with respect to three biosimilars (excluding ustekinumab), and entered into an agreement with Advanz for Europe for five biosimilars month.

A pre-filled pen presentation of Janssen-Cilag’s Stelara® (ustekinumab) injection (90mg/1mL and 45mg/0.5mL) has been listed on the Australian Register of Therapeutic Goods.

On 31 October 2023, the FDA approved Amgen’s Wezlana® (ustekinumab-auub), as the first FDA-approved biosimilar to Janssen’s Stelara®.  Wezlana is approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis (each in both adults and paediatric patients six years and older), and the treatment of moderately to severely active Crohn’s disease and moderately to severely active ulcerative colitis (in adults).  Wezlana® is a subcutaneous injection in a 45mg/0.5mL pre-filled syringe and a 45mg/0.5mL vial. 

It has been reported that the Munich Regional Court has issued a preliminary injunction against Formycon’s manufacture of FYB202, its Stelara® (ustekinumab) biosimilar, in Germany until expiry of Janssen’s SPC on its basic ustekinumab patent on 20 July 2024.  According to the reports, the decision reflected the arguments submitted by Janssen that in order to rely on the EU manufacturing waiver to export FYB202 before SPC expiry, Formycon was required to produce a relevant marketing authorisation in a country outside the EU in which the SPC was not in force, and had not done so.

FYB202 is not approved in the EU.  Formycon and its commercialisation partner Fresenius Kabi announced in September 2023 that their MAA for FYB202 has been accepted for review by the EMA.

Samsung Bioepis presented new data on its SB17 (ustekinumab, biosimilar to Janssen’s Stelara®) and Imraldi® (adalimumab, biosimilar to AbbVie’s Humira®) at the European Academy of Dermatology and Venereology (EADV) Congress.  The SB17 phIII study demonstrates that SB17 has equivalent efficacy and comparable safety and PK to Stelara® up to week 28 in patients with moderate to severe plaque psoriasis.  The Imraldi® four-year follow up study indicates that Imraldi can be started or transitioned from AbbVie’s Humira® (adalimumab) in patients with moderate-to-severe psoriasis.

On 11 September 2023, Sandoz and Samsung Bioepis entered an exclusive commercialisation agreement for SB17 in the US, Canada, EEA, Switzerland and the UK.

Business Korea reported that Celltrion filed an application with Australia’s Therapeutic Goods Administration (TGA) for approval of CT-P43, its biosimilar to Janssen’s Stelara^® (ustekinumab).   Celltrion applied for approval of all Stelara^® indications, including plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.

Celltrion submitted its aBLA for CT-P43 to the US FDA in June 2023 (and reached a settlement and licence agreement with Johnson & Johnson (J&J) permitting Celltrion to launch CT-P43 in the US on 7 March 2025), and submitted its MAA to EMA in May 2023.

The Canadian Federal Court upheld a decision of Canada’s Office of Submission and Intellectual Property (OSIP) to refuse Janssen’s application to list Canadian Patent 3113837 (‘837 patent) on the PMNOC register for two supplementary new drug submissions relating to Stelara® (ustekinumab) OSIP refused the application as the ‘837 patent application was filed in Canada after the submissions.

Health Canada approved ulcerative colitis as an indication for Stelara® on 27 January 2020.

As previously reported, on 22 May 2023 the US District Court of Delaware dismissed Janssen’s patent infringement case against Amgen pertaining to its Stelara® (ustekinumab) biosimilar with prejudice on the basis that each party bears its own costs. The proposed orders made it clear that the parties had settled.

Reuters has since reported a statement by Amgen that the ustekinumab settlement will permit Amgen to sell its biosimilar “no later than January 1^st, 2025”, suggesting the permitted launch date may be earlier than 1 January 2025.  As the API patent, one of six patents Janssen asserted in the proceedings, expires on 25 September 2023, we speculate that the agreed launch date is some time between 25 September 2023 and 1 January 2025.

The US District Court of Delaware has dismissed with prejudice Janssen’s patent infringement case against Amgen pertaining to its Stelara® (ustekinemab) biosimilar.  The parties agreed to dismiss the action with prejudice and each party will bear its own costs, expenses and attorney’s fees, and the proposed orders state the parties have agreed to settle the litigation.

Janssen commenced these proceedings against Amgen in November 2022 in relation to the API and MOT (UC) patents, and filed a motion for preliminary injunction in March 2023 (following dismissal of an earlier application due to non-compliance with the Court’s page limit requirements).

Formycon AG announced the successful conclusion of its extended Phase I clinical study comparing the pharmacokinetics of FYB202 and the reference drug Stelara® (ustekinumab).  This follows Formycon’s report in August 2022 that its Phase III studies demonstrated the comparable efficacy of FYB202 and Stelara® in patients with moderate-to-severe psoriasis vulgaris (plaque psoriasis).  Formycon stated FYB202 was bioequivalent to the reference drug Stelara® sourced in the EU as well as in the U.S. for all primary endpoint parameters.

EU and US regulatory submissions are still planned for the third quarter of 2023.  The product will be sold by Fresenius Kabi in key global markets.

Samsung filed a notice of opposition to the grant of Janssen’s Australian patent application AU2019346134 for the treatment of ulcerative colitis using an anti-IL12/IL23 antibody including Stelara® (ustekinumab).  Samsung’s Statement of Grounds and Particulars in support of the opposition are due to be filed with the Australian Patent Office by 12 July 2023.

We recently reported on Samsung’s Phase I clinical studies for SB17, its biosimilar to Janssen’s Stelara®.

Samsung announced that its Phase I clinical studies for SB17, biosimilar to Stelara® (ustekinumab), demonstrated pharmacokinetic bioequivalence and comparable safety, tolerability, and immunogenicity to reference ustekinumab in healthy volunteers.   Samsung will present these results at the 2023 American Academy of Dermatology (AAD) Annual Meeting held in New Orleans, March 17-21, 2023.

Alvotech announced clinical studies support biosimilarity and comparability of its ATV04 (ustekinumab biosimilar) and Johnson & Johnson’s Stelara®.  The data will be presented at the American Academy of Dermatology Annual Meeting on 17-21 March in New Orleans.

EMA accepted Alvotech’s MAA for AVT04 in February 2023, and the FDA accepted a BLA for AVT04 in January 2023.

Janssen Biotech, Inc. has filed a redacted, public version of its opening brief in support of its motion for a preliminary injunction in proceedings relating to Amgen’s Stelara® (ustekinemab) biosimilar.  Janssen is seeking to enjoin Amgen, Inc. from manufacturing and using in commercial quantities, offering to sell, selling within the United States, or importing for commercial purposes into the United States its ABP 654 biosimilar product.  We previously reported that Janssen initially asserted two patents: US Patent Nos 6,902,734 (API) and 10,961,307 (methods of treating ulcerative colitis).  In its redacted brief Janssen states that while it has also asserted four ‘manufacturing’ patents, it is seeking a preliminary injunction for the duration of the proceedings based on only two of these: US Patent Nos 9217168 and 9475858.  We also previously reported that Janssen refiled its preliminary injunction motion after its original motion was denied because it did not comply with the court’s page limit requirements.

Janssen Biotech, Inc. has filed another motion for a preliminary injunction against Amgen regarding its ustekinemab biosimilar, after its original motion was denied by US District Court Judge Noreika on 2 March 2023.  Janssen is seeking to enjoin Amgen, Inc. from manufacturing and using in commercial quantities, offering to sell, selling within the United States, or importing for commercial purposes into the United States its ABP 654 biosimilar product. 

As we previously reported, Judge Noreika had denied Janssen’s motion because it did not comply with the court’s page limit requirements.  Her Honour orally ordered that the motion could be re-filed in compliance with court requirements. 

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Janssen announced its positive long-term safety and clinical data for Stelara® (ustekinumab) in Chron’s disease and ulcerative colitis (five and four years respectively) at the ECCO Congress.  The findings indicate that key safety events were similar between a placebo and Stelara®.  The data demonstrated that of the patients with moderate to severe ulcerative colitis who achieved clinical response and continued treatment with Stelara® for 200 weeks – 58% were in clinical remission and 80% were in clinical response.  

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On Thursday, US District Court Judge Noreika denied a motion filed by Janssen Biotech, Inc (a Johnson & Johnson subsdiary) for a preliminary injunction regarding Amgen’s ustekinemab biosimilar, because the motion did not comply with the court’s page limit requirements.  We previously reported that Janssen commenced proceedings against Amgen in the US District Court (District of Delaware) in November 2022, asserting infringement of two patents, US 6902734 (ustekinemab compound) and US 10961307 (use of ustekinemab for the treatment of ulcerative colitis).   Judge Noreika ordered that the motion may be refiled in compliance with court requirements, so the consequences of the denial may be short-lived.   Janssen’s original Complaint states that Amgen had notified Janssen of its intention to commence marketing its Stelara® biosimilar on 6 May 2023 or as soon as it received FDA approval thereafter.

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.”

Janssen sued Amgen in the District Court of Delaware in relation to Amgen’s ABP654 (biosimilar ustekinumab).  Janssen alleges that Amgen’s product will infringe US patent Nos 6,902,734 (API) and 10,961,307 (methods of treating ulcerative colitis).  Amgen released preliminary results from its Ph III trials of ABP654 in April 2022, and it has not yet been approved by the FDA.

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.

BioFactura has announced successful completion of its Ph I trials relating to biosimilar ustekinumab candidate BFI-751.  The trial in Australia and New Zealand involved 226 subjects and demonstrated bioequivalence of BFI-751 to the US and EU versions of Janssen’s Stelara.  BioFactura now intends to conduct a Ph III confirmatory safety and efficacy trial in patients.

Janssen announced that the FDA has approved Stelara® (ustekinumab) for the treatment of paediatric patients aged six and over with active psoriatic arthritis (PsA).  As there were insufficient paediatric patients with PsA to conduct clinical trials, the FDA based its approval on phase III trials in adults and children with plaque psoriasis and adults with PsA.

Janssen’s Stelara® (ustekinumab): requesting a General Schedule Authority Required listing of a new form for the treatment of patients with Crohn disease and chronic plaque psoriasis

Formycon published its Q1 2022 financial results, reporting sales and other earnings of EUR 8.2 million.  Formycon also announced the addition of two biosimilar projects to its pipeline, FYB208 and FYB209, for undisclosed products.  Late stage Formycon development programs include biosimilars to Lucentis® (ranibizumab), Stelara® (ustekinumab) and Eylea® (aflibercept). Formycon plans to launch its biosimilar to Lucentis® (ranibizumab) in the second half of 2022.

Janssen announced data from two new analyses of Stelara® (ustekinumab) for the treatment of adults with Crohn’s disease and ulcerative colitis. Janssen reported that the data from these analyses provides additional support for Stelara® as a first-line option for Crohn’s disease and ulcerative colitis.

Janssen announced the submission of a sBLA to the FDA seeking expanded approval of Stelara® (ustekinumab) to treat paediatric patients aged 5 years and older with juvenile psoriatic arthritis.

Australia’s PBAC recommended the listing of Amgen’s Mvasi® (biosimilar bevacizumab). The PBAC also recommended listing Keytruda® (pembrolizumab) for the first line treatment of unresectable or metastatic mismatch repair deficient colorectal cancer and recommended listing Stelara® (ustekinumab) for the treatment of paediatric patients with severe chronic plaque psoriasis.

Janssen announces the FDA approved an additional indication for Stelara® (ustekinumab) for paediatric patients with skin lesions or moderate to severe plaque psoriasis.

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.

Janssen announces it has discontinued its Ph III LOTUS study of Stelara® (ustekinumab) in Systematic Lupus Erythematosus due to lack of efficacy.

Janssen announces approval of additional indication of ulcerative colitis for Stelara® (ustekinumab) in Japan.

Health Canada approves ulcerative colitis as an additional indication for Stelara®.

The UK’s NICE announces it will not recommend Stelara® for moderately to severely active ulcerative colitis due to uncertainties over cost-effectiveness.

NeuClone announces completion of patient recruitment and dosing in Ph I trials of ustekinumab biosimilar.

Janssen announces EC approval for additional indication for Stelara®. Stelara® is now indicated for the treatment of ulcerative colitis.

Alvotech and Fuji Pharma announce exclusive agreement for the commercialisation of Stelara® biosimilar in Japan. Alvotech will be responsible for development and supply while Fuji Pharma will receive exclusive rights to commercialise the drug in Japan. This follows Fuji Pharma’s recent US $50 million investment in Alvotech.

Australia’s NeuClone announces preclinical results for its biosimilar ustekinumab, which are now scheduled for Ph 1 clinical trials in 2019.