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2024
On 8 April 2024, Samsung Bioepis released its fifth US Biosimilar Market Report. The quarterly report details average sales price information for US launched biosimilars and market share and price trends.
The Q2 2024 Report notes that as of April 2024, the FDA has approved 48 biosimilars, with three of those (Alvotech’s/Teva’s Simlandi® (Humira®, adalimumab), Sandoz’s Jubbonti®/Wyost® (Prolia®/Xgeva®, denosumab) and Fresenius Kabi’s Tyenne® (Actemra®, tocilizumab) approved in the last quarter. 38 of the 48 approved biosimilars have launched in the US.
Samsung Bioepis reports that, on average, biosimilars in the US have gained 53% market share within 3 years post initial launch. As at Q4 2023, the adalimumab biosimilars share of the US adalimumab market was 4%, although this was up 2% compared with last quarter. The first biosimilar was launched in January 2023 (Amjevita™, Amgen) and multiple additional biosimilars entered the US market in July 2023.
On 5 March 2024, the FDA approved Fresenius Kabi’s Tyenne® (tocilizumab), biosimilar to Genentech’s/Roche’s Actemra®, for the treatment of rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. Tyenne® is the second FDA-approved tocilizumab biosimilar, following the approval of Biogen’s IV formulation Tofidence® in September 2023, but is the first approved subcutaneous formulation. Tyenne® was approved by the FDA in both IV and subcutaneous forms. The US launch date for its tocilizumab products remains confidential following a patent settlement with Roche and Chugai in October 2022.
Tyenne® has launched in more than 10 countries to date, including in Europe in November 2023 in both IV and subcutaneous formulations. Fresenius reports that its global roll out will continue through 2024 and 2025.
On 28 February 2024, Celltrion announced that it filed an application with MFDS for CT-P47, biosimilar to Genentech’s Actemra® (tocilizumab). The application seeks registration across the full Actemra® label and is based on Phase 3 results confirming equivalence of CT-P47 to Actemra®. Celltrion announced that it will use these results to accelerate applications for product approvals in other countries.
This follows Celltrion’s announcement on 13 February 2024 that it submitted a Marketing Authorisation Application to the EMA for CT-P47. On 28 January 2024, Celltrion also announced it had submitted a BLA in the US for CT-P47.
On 13 February 2024, Korea IT Times reported that Celltrion has submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for CT-P47, biosimilar to Actemra® (tocilizumab).
This follows the announcement by Celltrion at the end of January 2024, that that it submitted its US BLA for CT-P47.
On February 12, 2024, Chugai, Genentech, and Hoffmann-La Roche filed a motion for voluntary dismissal of their appeals regarding the Patent Trial and Appeal Board’s (PTAB) decision in IPR2022-00578 and IPR2022-00579. The motion records that Celltrion (the petitioner) has not formally agreed to the dismissal and may file a response.
Previously, Celltrion filed inter partes review (IPR) petitions IPR2022-00578 against Chugai/Genentech/Roche’s MOT (RA) patent no. US8580264 (‘264), and IPR 2022-00579 against Chugai/Roche’s device patent no. US10874677 (‘677). The PTAB concluded that claims 1-12 of the ‘264 MOT patent and claims 1-8 of the ‘677 patent are invalid in view of the prior art. Chugai, Genentech, and Hoffmann-La Roche appealed PTAB’s decision and are now seeking to have that appeal dismissed.
Celltrion announced that it has submitted a Biologics License Application (BLA) for CT-P47, biosimilar to Genentech’s Actemra® (tocilizumab), to the FDA. Celltrion is seeking approval for CT-P47 in both intravenous and subcutaneous formulations. Biogen received FDA approval for Tofidence®, its biosimilar Actemra® on 30 September 2023. On 1 August 2022 the FDA accepted Fresenius Kabi’s BLA for its tocilizumab biosimilar.
On 14 December 2023, Celltrion revealed that its phase III clinical trial of CT-P47 demonstrated equivalence with Actemra® in patients with rheumatoid arthritis.
On 18 January 2024, a phase 3 study, published in The Lancet Rheumatology, sponsored by Bio-Thera and Biogen concluded that BAT1806 (tocilizumab biosimilar) was equivalent in efficacy, safety, immunogenicity, and pharmacokinetic in comparison to Roche’s RoActemra®(tocilizumab). The study was randomized, double-blinded, multicenter, and multinational. It consisted of a 24-week initial treatment period (TP1), a 24-week secondary treatment period (TP2), and an extra 4-week follow-up period. In total there were 621 participants out of which 309 were assigned to the reference tocilizumab group and the rest 312 were assigned to the BAT1806 group.
On 16 January 2023, Bio-Thera Solutions announced that China’s NMPA approved its BAT1806 for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.
2023
Celltrion revealed in a corporate filing with the Repository of Korea’s Corporate Filings (DART) that its phase III clinical trial of CT-P47, biosimilar to Genentech’s Actemra®/Roactemra® (tocilizumab), demonstrated equivalence with the originator product in patients with rheumatoid arthritis. Celltrion confirmed it intends to apply for approval for all indications that Actemra®/Roactemra® is approved for. On 31 May 2023 Celltrion released its phase I data for CT-P47.
Fresenius Kabi announced it has launched Tyenne®, the first EC-approved biosimilar to Roche’s Actemra®/RoActemra® in the EU. Tyenne® was approved by the EC on 19 September 2023 to treat rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis, cytokine release syndrome and COVID-19.
Roche, Genentech, Chugai and Biogen have settled their dispute in the US District Court for the District of Massachusetts regarding Genentech’s Actemra® (tocilizumab) patents. Roche, Genentech and Chugai instigated proceedings on 23 July 2023, alleging that Biogen’s product, manufactured in China by Bio-Thera, infringed 20 US patents including US patent No 7521052 (method of treating rheumatoid arthritis) and US patent No 8398980 (IL-6R antibody subtype).
Biogen received FDA approval for Tofidence®, its biosimilar to Roche’s Actemra®/ RoActemra® on 30 September 2023, the only approved biosimilar tocilizumab in the US.
Biogen announced that the FDA has approved Tofidence®, its biosimilar to Roche’s Actemra®/ RoActemra® (tocilizumab) for treatment of moderately to severely active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis. Tofidence® is the first FDA approved tocilizumab biosimilar.
On 19 September 2023, the European Commission approved Fresenius Kabi’s Tyenne®, also a biosimilar to Roche’s Actemra® / RoActemra®, which is the first EU approved biosimilar to tocilizumab.
Fresenius Kabi announced that its Tyenne® (tocilizumab), biosimilar to Roche’s Actemra® / RoActemra® has been approved by the European Commission (EC) for the treatment of rheumatoid arthritis, active systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, chimeric antigen receptor T cell-induced cytokine release syndrome, and COVID-19. Tyenne® is the first biosimilar to Actemra® / RoActemra® approved by the EC.
The CHMP issued a positive opinion recommending approval of Tyenne® on 21 July 2023.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for three biosimilars:
- Fresenius Kabi’s Tyenne® (tocilizumab), biosimilar to Roche’s Actemra® / RoActemra®. Tyenne® is intended for the treatment of rheumatoid arthritis, active systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, chimeric antigen receptor T cell-induced cytokine release syndrome, and COVID-19. Tyenne is the first biosimilar for this active substance.
- Sandoz’s Tyruko® (natalizumab), biosimilar to Biogen’s Tysabri®. Tyruko® is intended to treat active relapsing remitting multiple sclerosis.
- BGP Pharma’s Yesafili® (aflibercept), a biosimilar to Regeneron’s Eylea®. It is intended to treat age-related macular degeneration
To obtain approval in Europe, the European Commission needs to approve the above positive recommendations from the CHMP.
During this same July 2023 CHMP meeting, the CHMP also issued a positive opinion for BMS’s Opdivo® (nivolumab) to treat completely resected stage IIB or IIC melanoma and Merck’s Keytruda® (pembrolizumab) to treat HER2-Positive Advanced Gastric or Gastroesophageal Junction.
Genentech, Inc., Hoffmann-La Roche, Inc. and Chugai Pharmaceutical Co Ltd sued Biogen MA Inc, and Bio-Thera Solutions, Ltd in the District Court of Massachusetts in relation to Biogen’s BIIB800, (biosimilar tocilizumab). Genentech alleges that Biogen’s product, manufactured in China by Bio-Thera, will infringe 20 US patents, including US patent No 7521052 (method of treating rheumatoid arthritis) and US patent No 8398980 (IL-6R antibody subtype). On 9 December 2022 Biogen announced that the FDA had accepted its aBLA for BIIB800.
A Hisun phase I study has demonstrated pharmacokinetic similarity and bioequivalence between HS628, a proposed tocilizumab biosimilar to Genentech’s Actemra®. The safety and immunogenicity profiles of HS628 were also found to be similar to the reference product in healthy Chinese male subjects. Actemra® is approved in the US for the treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis patients. The study also notes that a phase III clinical trial is currently underway to compare the efficacy and safety of HS628 and Actemra® in patients with moderate to severe RA.
On 5 June 2023, Dr Reddy’s announced a successful phase I study of its biosimilar to Actemra®.
Dr Reddy’s Laboratories announced completion of a successful phase I clinical trial of DRL_TC, its biosimilar to Genentech’s Actemra® (tocilizumab) by intravenous route. The study demonstrated the pharmacokinetic equivalence, safety, and immunogenicity of DRL_TC compared to the reference products (US sourced Actemra® and EU sourced RoActemra®), confirming similarity in pharmacodynamic parameters and no notable differences in safety and immunogenicity.
In December 2022, Dr Reddy’s announced successful phase I trial of DRL_TC by subcutaneous route.
Celltrion has released its clinical phase I data for its tocilizumab product CT-P47, biosimilar to Roche’s Actemra® which it announced at the 2023 European Congress of Rheumatology (2023 EULAR). Celltrion has successfully demonstrated pharmacodynamic equivalence and safety comparable to Actemra®.
Last week Celltrion filed MAA with EMA for biosimilar to Janssen’s Stelara® (ustekinumab).
A study published in Frontiers in Pharmacology has found that the pharmacokinetic characteristics and immunogenicity of Livzon Mabpharm’s LZM008 were similar to Genentech’s ACTEMRA®. The safety profiles of LZM008 were similar in two groups with mild–moderate adverse effects. The study was a randomised, double-blinded, single-dose, parallel-group phase I clinical trial conducted in Huashan Hospital and Wuxi People’s Hospital in China. The incidence of treatment emergent adverse events was comparable in LZM008 and ACTEMRA® groups (98% versus 100%). The study was funded by the Livzon Mabpharm Inc. and the Ministry of Science and Technology of China.
In February 2023, Fresenius Kabi demonstrated bioequivalence for its tocilizumab biosimilar.
A new Fresenius Kabi study published in the Expert Review of Clinical Immunity has confirmed pharmacokinetic bioequivalence between a tocilizumab biosimilar and a US-licensed tocilizumab (Actemra®). The authors also found that the safety profiles were similar. Tocilizumab is prescribed for autoimmune conditions including rheumatoid arthritis.
Australia’s PBAC recommended amending the circumstances under which Roche’s Actemra® (tocilizumab) is available for reimbursement via the PBS. The new PBS listing of Actemra includes ultrasound in the clinical criteria as a method for diagnosis of giant cell arteritis.
Bio-Thera Solutions announced that China’s NMPA has approved BAT1806 (biosimilar tocilizumab) for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.
2022
Dr Reddy’s announced that DRL_TC (biosimilar tocilizumab) met is primary and secondary endpoints in Ph I trials. Dr Reddy’s is developing DRL_TC in both subcutaneous and intravenous formulations.
Biogen announced that the FDA accepted its aBLA for BIIB800 (biosimilar tocilizumab) referencing Genentech’s Actemra®. This follows the EMA acceptance of Biogen’s MAA for BIIB800 in September 2022. Tocilizumab is an anti-interleukin-6 receptor monoclonal antibody which is indicated for various health conditions including moderate to severe RA in adults as well as juvenile idiopathic polyarthritis and systemic juvenile idiopathic arthritis.
Australia’s PBAC reversed the temporary COVID measures put in place in response to drug shortages during the COVID pandemic allowing patients to transition off tocilizumab during the shortage period to another biological disease modifying drug (bDMARD) claiming that “as of 15 July 2022, the supply shortage of tocilizumab has resolved”. From 01 December 2022, these items will move to a ‘Supply Only’ state for six months (allowing patients to fill outstanding repeats on prescriptions), before being completely removed from the PBS.
Roche Canada announced that Health Canada has approved Actemra® IV (tocilizumab) for the treatment of hospitalised adult patients with COVID-19 who are receiving systemic corticosteroids, and require supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation.
In October 2022, Fresenius Kabi entered into a confidential settlement agreement with Chugai and Roche, which resulted in the termination of seven Inter Partes Review proceedings in relation to tocilizumab patents. The IPRs were commenced by Fresenius in 2021 and 2022. At the time of settlement, the PTAB had instituted six of the IPRs, with one pending institution. The IPRs were IPR2021-01024, IPR2021-01025 , IPR2021-01288, IPR2021-01336, IPR2021-01542, IPR2022-00201 and IPR2022-01065.
The PTAB instituted Celltrion’s two inter partes reviews (IPRs) of Chugai and Roche’s tocilizumab patents 8,580,264 and 10,874,677. The IPRs were instituted on each of the grounds in Celltrion’s petition.
Fresenius Kabi announced that the EMA has accepted its MAA for MSB11456 (biosimilar tocilizumab). The application includes clinical data for both subcutaneous and IV administrations.
Fresenius Kabi announced that the FDA has accepted for review Fresenius’ biosimilar candidate MSB11456 to Chugai’s Actemra® (tocilizumab). Actemra is presently the only tocilizumab product on the market in the US.
Korea Biomedical Review reported that Celltrion has received approval from Poland’s Pharmaceutical and Medical Equipment Registration Office (URPL) for its IND for Ph III trials of CT-P47 (biosimilar to Actemra®, tocilizumab).
The PTAB instituted an inter partes review filed by Fresenius Kabi against US Patent 9,750,752 (‘752 patent) owned by Chugai Seiyaku Kabushiki Kaisha and Hoffman-La Roche. The ‘752 patent is directed at methods of treating giant cell arteritis by subcutaneously administering tocilizumab. This is the sixth IPR instituted by PTAB regarding tocilizumab patents arising from Fresenius Kabi challenges.
Korea Biomedical Review reported that Celltrion has submitted a global Ph III clinical trial plan for CT-P47 (biosimilar tocilizumab) to Poland’s Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. The global Ph III trial commenced in May 2022, and follows the phase 1 trial which commenced in July 2021.
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.
2021
Theramex and Enzene Biosciences announced that they have entered into an agreement for the development and commercialisation of biosimilar tocilizumab. The product will be available in parenteral vials, PFS and autoinjectors from 2026 in Europe, the UK, Switzerland and Australia.
Fresenius Kabi announced that its biosimilar tocilizumab candidate MSB11456 successfully met its primary and secondary endpoints in Ph I trials of both subcutaneous and intravenous formulations.
Hetero announced that it has received emergency use approval from India’s DCGI to market its biosimilar tocilizumab for the treatment of COVID-19.
Roche notified Australia’s TGA of shortages of multiple presentations of Actemra® (tocilizumab). Tocilizumab has been used off-label for COVID-19, driving global demand. The TGA made a number of recommendations for patients currently treated with Actemra®, including switching to alternative biological disease modifying drugs.
ThePrint reported that Hetero Labs has submitted an application to start clinical trials and manufacture of biosimilar tocilizumab in India. Tocilizumab has been recommended for off-label use in the treatment of COVID-19 by the Indian Government, but has been subject to extreme shortages. The product is manufactured by Roche and distributed in India by Cipla pharmaceuticals. It is not known whether Hetero has reached a licensing agreement with Roche.
Biogen announced it has reached an agreement with Bio-Thera for the development, manufacture and commercialisation of BAT1806 (proposed tocilizumab biosimilar). Under the agreement, Biogen will gain exclusive rights to BAT1806 in all countries excluding China.
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.
2020
Gedeon Richter announces it has entered an asset purchase agreement with Mycenax Biotech for the purchase of a biosimilar tocilizumab product. Under the agreement, Richter will receive worldwide rights to develop, manufacture and commercialise the product which is expected to reach global markets in 2025.
2019
Bio-Thera announces commencement of Ph III trials of BAT1806, its proposed tocilizumab biosimilar. Results are expected in the second half of 2020.
2018
Mycenax announces positive results from Ph I PK clinical trials, reporting the product met the primary endpoint in PK comparison.
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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