BioBlast w/e 01 Sep 23

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.

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.

Outlook Therapeutics announced the FDA issued it with a Complete Response Letter (CRL) for its BLA for ONS-5010, biosimilar to Genentech’s Avastin® (bevacizumab). The FDA acknowledged the NORSE TWO pivotal trial met its safety and efficacy endpoints, but could not approve the BLA due to several chemistry, manufacturing and controls issues, as well as open observations from pre-approval manufacturing inspections and a lack of substantial evidence.

On 28 October 2022, the FDA accepted Outlook Therapeutics’ BLA for ONS-5010 for the treatment of wet age-related macular degeneration. The FDA has set a PDUFA goal date of 29 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.

On 1 July 2023, Yuflyma® became commercially available in the US after Celltrion obtained a licence from AbbVie on 27 April 2022.

Alvotech published its first half 2023 financial results, reporting a revenue growth to $22.7M for the six months ending 30 June 2023, compared to $3.9M for the same six months of 2022.  Revenue for that period consisted of product revenue from sales of AVT02 (Alvotech’s adalimumab biosimilar) in select European countries and Canada.  As of 30 June 2023 the company has $60.5M in cash/equivalents (excluding $25.2M in restricted cash) and current borrowings of $808.6M.  Its R&D costs for the six month period ending 30 June 2023 were $99.6M.

Recent highlighted reported included Alvotech’s expanded partnership with Advanz Pharma, adding five biosimilar candidates which Advanz Pharma will commercialise in Europe; Alvotech and Teva’s settlement and license agreement with Johnson & Johnson concerning AVT04, Alvotech’s proposed biosimilar to Stelara® (ustekinumab); a complete response letter (CRL) from the US Food and Drug Administration (FDA) for Alvotech’s second Biologics License Application (BLA) for AVT02, an interchangeable high-concentration adalimumab biosimilar; and its expanded strategic partnership agreement with Teva, including exclusive commercialisation rights in the US by Teva for two new biosimilar candidates developed by Alvotech, as well as line extensions of two current biosimilar candidates.

The Patent Trial and Appeal Board (PTAB) issued decisions in Celltrion’s two inter partes reviews (IPRs) (IPR2022-00578 and IPR2022-00579), finding Chugai and Roche’s tocilizumab patents (US patent nos. 8,580,264 and 10,874,677) were invalid.  The PTAB found that claims 1-12 of the ‘264 patent were anticipated and/or obvious, and claims 1-8 of the ‘677 patent were obvious. 

The PTAB instituted Celltrion’s two IPRs of Chugai and Roche’s tocilizumab patents on 31 August 2022.

The Korea Herald reported that Dong-A ST submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for its Stelara® biosimilar DMB-3115.  DMB-3115 was jointly developed by Dong-A and Meiji Seika Pharma, and will be commercialised in Europe by the Intas subsidiary Accord Healthcare.

Dong-A published the results of its global Ph III trials of DMB-3114 in January 2023.

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®.

Merck announced that the European Commission has approved a new indication for Keytruda® (pembrolizumab) – first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Scope [CPS]≥1), in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy.

Merck stated that Keytruda® is the first immunotherapy approved in the EU for the first-line treatment of this patient population.  Keytruda is approved globally for the treatment of a large range of cancers.  In June 2022 the EC approved Keytruda® for expanded melanoma indications.

Formycon and Klinge Biopharma announced that the FDA has accepted for review the BLA for FYB203, biosimilar to Regeneron’s Eylea® (aflibercept).  The FDA has assigned a target action date of June 2024.

Formycon submitted the BLA for FYB203 in June 2023.  FYB203 is being developed by Formycon and will be commercialised by Klinge Biopharma.

AbbVie announced that it has submitted applications to the FDA and EMA for a new indication for Skyrizi® (risankizumab) to treat moderately to severely active ulcerative colitis (UC).  Skyrizi® is currently approved by both regulatory authorities to treat Crohn’s disease, psoriatic arthritis and psoriasis.

Bristol Myers Squibb announced that the FDA has approved Reblozyl® (luspatercept-aamt) to treat anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.  Reblozyl® is the first and only therapy that has demonstrated better patient outcomes compared to an ESA in MDS-related anemia.

On 1 May 2023, BMS announced that the FDA has accepted its sBLA, and the EMA has validated its Type II Variation Application for Reblozyl® (luspatercept-aamt) to treat the above patient group.