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2024
On 5 March 2024, a study published in Modern Rheumatology found that LG Chem’s LBEC0101, the biosimilar of etanercept, matches up to the reference product in terms of effectiveness and safety in the real-world treatment of rheumatoid arthritis. This evidence was gathered from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients treated between 2015 and 2021. The study reports that patients who switched from the reference product to LBEC0101 did not experience any significant differences in their treatment outcomes.
A study by the Italian University of Bologna published in Springer Link’s Clinical Drug Investigation, found that Sandoz’s GP2015 (etanercept biosimilar), Samsung Bioepis’ SB4 (etanercept biosimilar) and Sandoz’s GP2017 (adalimumab biosimilar) have equivalent effectiveness over a long period of time, compared to originator medicines etanercept and adalimumab respectively. The study recruited a total of 1598 patients with rheumatoid arthritis and monitored them for over 48 months during treatment.
2023
mAbxience announced it has entered a licence agreement with Intas Pharmaceuticals, under which Intas will gain the right to commercialise etanercept (biosimilar to Amgen’s Enbrel®) in more than 150 countries including Europe and the US for various autoimmune disorders. mAbxience (majority owned by Fresenius Kabi, partially owned by Insud Pharma) will develop, manufacture and supply the etanercept biosimilar.
On 20 September 2023, mAbxience reached an agreement with Abbott to commercialise several biosimilars focusing on oncology, women’s health and respiratory diseases in emerging markets in Latin America, Southeast Asia, the Middle East and Africa.
A study published in Reumatismo found that Samsung Bioepis’ SB4, biosimilar to Amgen’s Enbrel® (etanercept), and Amgen’s ABP501, biosimilar to AbbVie’s Humira® (adalimumab) both have similar safety profiles to their respective originator products in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The study also found that there was a reduced biosimilar retention rate at 24 months. It concluded that biosimilars “could be considered a valid, safe, and less expensive alternative to originators”.
A Sandoz study published in Drug Safety found that eight Sandoz biosimilars (adalimumab (Hyrimoz®), epoetin alfa (Binocrit®), etanercept (Erelzi®), filgrastim (Zarzio®), infliximab (Zessly®), pegfilgrastim (Ziextenzo®), rituximab (Rixathon®), and somatropin (Omnitrope®) “can be used as safely as their respective reference biologics” based on real-world experience of all eight marketed products. The study summarised post-approval cumulative patient exposure and safety experience for the eight products based on the available pharmacovigilance data from Periodic Safety Update Reports (PSURs) and the corresponding PSUR assessment reports authored by health authorities, where available, as of 31 January 2023. The authors also concluded that “it is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA)”.
The FDA approved Amgen’s Enbrel® (etanercept) on 18 October 2023 for a new indication: active juvenile psoriatic arthritis (JPsA) in paediatric patients 2 years of age and older.
On 21 March 2023, one of the largest studies to date examining etanercept biosimilar/originator outcomes found that Biogen’s Benepali® and Novartis’ Erelzi® demonstrated comparable efficacy to Enbrel®. Erelzi® was the first etanercept biosimilar approved by the FDA on 30 August 2016, with Samsung Bioepis’ Eticovo® (marketed as Benepali® in Europe) receiving FDA approval on 25 April 2019.
An FDA meta-analysis found that there are no differences in safety profiles or immunogenicity rates in patients who switched to biosimilars compared to those who remained on an originator biologic or biosimilar. Biologics assessed in the study include adalimumab, epoetin alfa-epbx, etanercept, filgrastim, infliximab, insulin glargine, rituximab, and trastuzumab.
On 18 September 2023, the FDA released its draft industry guidance for biosimilar and interchangeable biosimilar product labelling.
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®).
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.
A new study published in Rheumatology has found that etanercept biosimilars (Biogen’s Benepali® and Novartis’ Erelzi®) demonstrated comparable efficacy to Pfizer’s Enbrel®. The study is one of the largest to date, and showed that biologic-naïve rheumatoid arthritis patients had similar outcomes in terms of survival and disease activity whether they received the originator or biosimilar treatment.
The study was supported by the British Society for Rheumatology.
2022
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.
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).
Lupin announced that Health Canada has approved Rymti® (biosimilar etanercept) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, axial spondylarthritis (including ankylosing spondylitis and non-radiographic axial spondylarthritis), plaque psoriasis and paediatric plaque psoriasis.
Alphapharm (Viatris’ Australian subsidiary) has its etanercept biosimilar, Nepexto®, on the agenda for the November PBAC meeting. If the PBAC recommends that Nepexto is PBS-listed, it will become the third PBS-listed etanercept product after Pfizer’s Enbrel® and Arrow’s Brenzys®.
Pfizer commenced patent infringement proceedings in the Federal Court of Australia against Samsung Bioepis, Merck, Organon and Arrow Pharmaceuticals in relation to AU2005280034 and the supply of etanercept.
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.
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.
2021
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.
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.
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 US Supreme Court declined to hear Novartis’ appeals against a lower court decision which upheld two Amgen patents relating to Enbrel® (etanercept). Keren Haruvi, President of Sandoz US and Head of North America estimates that a biosimilar etanercept in the US could have saved payees USD$1 billion annually.
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.
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.
2020
Lupin receives approval for biosimilar etanercept in Australia under the trade names Etera® and Rymti® in PFS presentations.
Merck announced Health Canada has approved Brenzys® (biosimilar etanercept) for four new indications:
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adult patients with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy
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pediatric patients ages 4 to 17 years with chronic severe PsO who are candidates for systemic therapy or phototherapy
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reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis and improving physical function in adult patients with psoriatic arthritis (PsA)
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reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients aged 4 to 17 years
Lupin and Mylan launch Nepexto® (biosimilar etanercept) in Germany. Nepexto® is indicated for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, severe axial spondyloarthritis and plaque psoriasis.
Pfizer releases its Q2 FY20 financial results. Pfizer reported a 16% decrease in international revenues for Enbrel® (etanercept), attributing this decrease to biosimilar competition in Europe, Japan and Brazil.
Sandoz responds to the US Court of Appeals judgment which upheld a ruling from the New Jersey District Court which declared the Amgen patents relating to (etanercept) valid. Sandoz stated that it will continue its efforts to make Erelzi® available in the US, and is evaluating its options, including a possible appeal to the US Supreme Court.
Mylan and Lupin announce EMA marketing authorisation for Nepexto® (etanercept) for all indications of the reference product Enbrel®.
Mylan and Lupin announce the EU’s CHMP has adopted a positive opinion recommending Nepexto® (etanercept) for all indications as Enbrel®.
Mundipharma announces commercialisation agreement with Samsung. The agreement grants Mundipharma exclusive commercialisation rights to Samsung’s adalimumab, etanercept, trastuzumab and bevacizumab candidates in Taiwan and Hong Kong.
Clover announces it has received approved to enter clinical trials in China with SCB-808, biosimilar etanercept.
2019
Lupin releases results of Ph III trials of etanercept biosimilar, reporting similarity with the reference product.
Amgen and pharmacy benefit manager Abarca announce outcome based agreement for Enbrel®, under which Amgen will provide rebates to Abarca’s clients who start etanercept to treat RA but discontinue treatment after 3 months. This is the second outcome-based between Abarca and Amgen, the prebvious (2018) arrangement related to hyperlipidemia medicine Repatha.
Sandoz releases results of Erelzi® studies, including interim results of the COMPACT study, and long-term cost savings modelling analysis.
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.
Celltrion presents pooled data from 3 post marketing studies of etanercept biosimilar, reporting that the study shows real-world evidence of the safety of the product.
Lupin announces plans to file applications for biosimilar etanercept in the US market by the fourth quarter of FY20.
Samsung Bioepis releases results of Benepali® psoriasis study, announcing results demonstrate the product’s effectiveness and safety in a real-world setting. The study was conducted by the British Association of Dermatologists, Biologics and Immunomodulators Registry and enrolled 269 patients with moderate to severe psoriasis.
Samsung Bioepis announces Brazilian approval for Brenzys®. For the first 10 years, Samsung Bioepis willl supply the drug to local distributors, during which a technology transfer with local partners will take place, allowing local partners to take over manufacturing after this period.
Quarterly etanercept data reveals biosimilar uptake remains slow in the Australian market. While the uptake of Brenzys® (MSD) has steadily grown, the biosimilar still only forms 15% of total scripts.
Sandoz announces US District Court ruled against Sandoz in patent litigation, preventing the launch of Erelzi®. Sandoz has announced that they will appeal this decision, and that both parties have agreed to an expedited appeal.
Samsung Bioepis announces Benepali® dominates 40% share in European etanercept biosimilar market.
Results of 24 week switching study released, citing no changes in safety or efficacy outcomes. The study was conducted in patients with moderate to severe rheumatoid arthritis and compared the outcomes of those who swapped to the Sandoz candidate at 24 weeks and those who continued with the reference drug.
In response to FDA approval of Eticovo®, Amgen and Roche file a suit alleging the infringement of five patents. Within the complaint, Amgen and Roche allege that Samsung failed to provide them with a copy of its aBLA or details of the manufacturing process, as well as failing to provide the 180 day notice of commercial marketing.
FDA approves biosimilar etanercept Eticovo® for all eligible indications (RA, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis and polyarticular juvenile idiopathic arthritis).
Lupin announces approval of biosimilar etanercept in Japan for the treatment of moderate to severe Rheumatoid Arthritis.
Health Canada approves new indication for Erelzi®, allowing for the treatment of psoriatic arthritis.
Clover announces that Phase I trials of a potential etanercept biosimilar are underway.
Lupin and Mylan announce agreement to commercialise etanercept biosimilar in Europe, Australia, New Zealand, Latin America, Africa and Asia.
Sandoz reports results of long term switching studies for biosimilars Zessly® (infliximab) and Erelzi® (etanercept) in RA.
Lupin announces that its MA application for biosimilar etanercept has been accepted for review by the EMA.
Lupin announced YL Biologics has filed a BLA for biosimilar etanercept (YBL113) in Japan. YL Biologics is a joint venture between Yoshindo and Kyowa (Lupin’s subsidiary), and YBL113 is the first biosimilar developed by the JV.
LG Chem (formerly LG Life Sciences) obtains Korean regulatory approval for biosimilar etanercept. This is the second biosimilar etanercept approved in Korea (after Samsung’s 2015 approval of Brenzys), and follows the Japanese approval of LG Chem’s biosimilar etanercept in January this year.
Lupin declares its intention to file an application in the EU and JP for biosimilar etanercept in July 2019.
GE announces it is building a FlexFactory (single use technology with 2 x 2000L bioreactors) facility in China for Clover, which is expected to be up and running by the end of 2018. Clover intends to manufacture biosimilar etanercept for the Chinese market there.
2017
The Australian government’s biosimilar uptake initiative results in changes to PBS listing for Samsung’s Brenzys® in Australia. “A” flagging (substitution at the pharmacy level) remains unchanged.
Sandoz’s biosimilar etanercept (Erelzi®) approved in Australia in 3 dosages, the second approved biosimilar etanercept.
Amgen announces US launch of new ENBREL Mini® single-dose prefilled cartridge with AutoTouch® reusable autoinjector.
EU |
EMA approves Erelzi®
Biosimilar etanercept (Erelzi®) approved in EU to treat multiple inflammatory diseases.
Sandoz receives a Notice of Compliance for Erelzi® for the treatment of moderately to severely active rheumatoid arthritis in adults with or without methotrexate and for reducing signs and symptoms of active ankylosing spondylitis. (Sandoz did not seek registration for psoriatic arthritis or plaque psoriasis).
Samsung’s biosimilar etanercept, Brenzys, is listed on the PBS in Australia with “A” flagging enabling substitution at the pharmacy level
2016
Samsung Bioepis receives positive CHMP opinion for its application for indication extension of Benepali® (etanercept) to include juvenile idiopathic arthritis and pediatric plaque psoriasis.
Brenzys®(SB4) is the first biosimilar etanercept to be approved in Canada.
US |
FDA approves Erelzi®
FDA approves Sandoz’s Erelzi® for all indications included in the reference product label, including rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and polyarticular juvenile idiopathic arthritis.
EMA approves Benepali®, biosimilar etanercept (SB4) for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and plaque psoriasis. CHMP positive opinion was announced on 20 Nov 2015. Samsung says it developed, tested and had its Benepali® approved in under 4 years.
2015
Samsung Bioepis announces Brenzys® (SB4), biosimilar etanercept received approval in South Korea with launch intended late 2015/early 2016.
Product specific reports based on extracts from our BioBlast® database
aflibercept | Eylea® | Regeneron
bevacizumab | Avastin® | Roche/Genentech
cetuximab | Erbitux® | BMS/Merck
darbepoetin | Aranesp® | Amgen
denosumab | Prolia®/Xgeva® | Amgen
dupilumab | Dupixent® | Sanofi-Aventis
eculizumab | Soliris® | Alexion
filgrastim (GCSF) | Neupogen® | Amgen
golimumab | Simponi® | Janssen
guselkumab | Tremfya® | Janssen
infliximab | Remicade® | Johnson & Johnson
ixekizumab | Taltz® | Eli Lilly
natalizumab | Tysabri® | Biogen/Elan
omalizumab | Xolair® | Genentech / Novartis
pegfilgrastim | Neulasta® | Amgen
pembrolizumab | Keytruda® | Merck
ranibizumab | Lucentis® | Genentech
regdanvimab | Regkirona® | Celltrion
risankizumab | Skyrizi® | AbbVie
rituximab | Rituxan®/MabThera® | Genentech/Biogen
secukinumab | Cosentyx® | Novartis
tocilizumab | Actemra® | Roche
trastuzumab | Herceptin® | Roche/Genentech
BioBlast® Editor and Contributing Author
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