Pearce IP BioBlast w/e 19 April 2024

On 21 April 2024, Swedish biosimilar developer Xbrane announced that the FDA issued a Complete Response Letter (CRL) regarding its BLA for ranibizumab biosimilar Xlucane^TM.  The issues identified primarily concern (a) the analytical methods for the reference standard; and (b) pre-approval inspections of manufacturing partner’s sites.  The FDA has not requested additional clinical studies to demonstrate biosimilarity and has not requested reinspection of any site.

Xbrane will subsequently announce a resubmission date for the ranibizumab BLA.

On 19 April 2024, Merck (known as MSD outside Canada and the US) announced that Health Canada has approved Keytruda® (pembrolizumab) as a 1^st line treatment for locally advanced unresectable or metastatic HER2 negative gastric cancer or gastroesophageal junction adenocarcinoma in combination with fluoropyrimidine and platinum-based chemotherapy.

Keytruda® was approved for the same indication in the US in November 2023 and in Korea in March 2024, while a positive CHMP recommendation was received in Europe in October 2023.

On 19 April 2024, Alvotech announced that it has entered a long-term agreement with an unnamed strategic partner to market in the US its high concentration interchangeable adalimumab-ryvk (AVT02), biosimilar to AbbVie’s Humira®, which received FDA approval in February 2023.  Teva will continue to commercialise adalimumab-ryvk under the SIMLANDI® brand in the US pursuant to its existing strategic partnership with Alvotech, which remains unchanged.

On 18 April 2024, Takeda announced FDA approval of subcutaneous administration of ENTYVIO® (vedolizumab) for maintaining therapy in adults with moderately to severely active Crohn’s disease (CD).

This follows the FDA’s acceptance of Takeda’s BLA for ENTYVIO® for the same indication, and the FDA’s approval of ENTYVIO® for ulcerative colitis (UC), in September 2023.

Vedolizumab biosimilars have previously been reported to be in development by Polpharma Biologics, Alvotech(under an agreement with Advanz) and Bio-Thera.

On 17 April 2024, Biocon announced that it signed an exclusive licensing and supply agreement for generic Ozempic® (semaglutide) in Brazil.  Biocon will develop, manufacture and supply the semaglutide product and Biomm is responsible for regulatory and commercialisation strategies in Brazil.

This follows news earlier this month that Hangzhou Jiuyan Gene Engineering’s application for a generic version of Ozempic® (semaglutide) was accepted by regulators in China.

On 16 April 2024, Alvotech announced the US has approved SELARSDI™ (ustekinumab-aekn), biosimilar to Stelara®(ustekinumab), for both adult and paediatric use. Selarsdi™ was developed by Alvotech and will be commercialised by Teva in the US.

This is the second US biosimilar approved under the strategic agreement between Teva and Alvotech, following the FDA approval of Simlandi® (adalimumab) as an interchangeable biosimilar to AbbVie’s Humira® in February.

SELARSDI™ can be launched in the US from 21 February 2025, following Alvotech’s and Teva’s ustekinumab settlement with Johnson & Johnson in June 2023.

The Korea Biomedical Review reports that, on 16 April 2024, Merck Sharp & Dohme (MSD) announced that it obtained approval in Korea for an expanded indication for its Keytruda® (pembrolizumab) as a combination therapy with chemoradiotherapy for treating FIGO (International Federation of Genecology and Obstetrics) 2014 stage III-IVA cervical cancer.

The same indication was approved in the US by the FDA in January 2024.  This followed the FDA approval in October 2021 for Keytruda® plus chemotherapy, with or without bevacizumab, as a treatment for patients with persistent, recurrent or metastatic cervical cancer whose tumours express PD-L1.

On 15 April 2024, Fresenius Kabi announced its US launch of Tyenne® (tocilizumab-aazg), biosimilar to Roche’s Actemra® (tocilizumab) in both intravenous and subcutaneous formulations.  These formulations were FDA approved on 5 March 2024.   Tyenne is the third biosimilar product Fresenius Kabi has launched in the US.

Fresenius Kabi launched Tyenne® in Europe as the first to market biosimilar in November 2023 in both IV and subcutaneous formulations.

The Korea Times reports that Celltrion presented the 78-week results of its Phase 3 study of CT-P41, biosimilar to Amgen’s Prolia® (denosumab), at the World Congress on Osteoporosis held in London from 11-14 April 2024.  It is reported that the clinical trial showed CT-P41 has equivalent efficacy, pharmacokinetics and safety to Prolia® in postmenopausal women with osteoporosis.

Celltrion applied to the FDA for marketing authorisation of CT-P41 in December 2023.  The first Prolia® (denosumab) biosimilar approved in the US was Sandoz’s Jubbonti®, on 5 March 2024.

Prolia® (denosumab) biosimilars have been approved in Canada (Sandoz’s Jubbonti® on 20 February 2024) and China (Boan Biotech’s Boyoubei® in November 2022 and Mabwell’s Mailishu® in March 2023).  Other companies have Prolia® biosimilars under development including Samsung Bioepis, Alvotech, Intas, and Shanghai Henlius Biotech.

As previously reported, on 27 December 2023, and in a judgment published on 31 January 2024, the US District Court for the Northern District of West Virginia held that Mylan and Biocon infringed eight claims of Regeneron’s US patent 11,084,865, in respect of formulations of aflibercept such as Eylea®. The Judge found asserted claims of two aflibercept method of treatment patents (11,253,572 and 10,880,601) to be invalid.  Regeneron appealed and Mylan and Biocon filed cross-appeals.

On 12 April 2024, the Court of Appeals for the Federal Circuit dismissed the appeal and cross-appeals on the basis that all parties agreed that the Appeals Court lacked jurisdiction pending a decision of all patents in dispute.  This was agreed because only three patents out of the 24 asserted by Regeneron had been addressed in the 27 December 2023 decision and the infringement and validity of numerous patent claims are still pending in the proceeding.

A hearing of Regeneron’s motion for a permanent injunction following the Court’s decision that Mylan/Biocon infringe US 11,084,865 is scheduled for 2 May 2024, ahead of a status conference on 13 May 2024.

On 11 April 2024, the United States Judicial Panel on Multijurisdictional Litigation ruled that patent infringement actions brought by Regeneron regarding aflibercept biosimilars by Amgen, Mylan, Celltrion, Samsung Bioepis (2 actions) and Formycon involved “common questions of fact” and should be centralized in the Northern District of West Virginia.

Regeneron commenced five of its actions in the Northern District of West Virginia but commenced proceedings against Amgen in the Central District of California.  The Amgen case will now be transferred and assigned to Judge Kleeh who is hearing the remainder of the actions.

There are 63 patents in issue across each of the six actions.  In each case, Regeneron alleges infringement of a common set of 13 US patents covering its ophthalmic drug, Eylea® (aflibercept).

Of the common set of 13 patents, one (a formulation patent, US 11,084,865, expiring in June 2027) was held by Judge Kleeh to be valid and infringed in a decision issued in the first-filed Mylan action in December 2023.  Seven of the patents are at issue in preliminary injunction proceedings due to be heard on 2 May 2024 in the Northern District of West Virgina actions against Celltrion, Samsung Bioepis and Formycon.

Boston-based Ginkgo Bioworks announced on 10 April 2024 an expansion of its partnership with global healthcare leader, Novo Nordisk. This extended collaboration, set to span five years, is targeting improving the manufacturing of Novo Nordisk’s medicines with a focus on chronic diseases including diabetes and obesity.

Ginkgo Bioworks, known for its expertise in cell programming and biosecurity, will bring its synthetic biology platform to optimize Novo Nordisk’s R&D pipeline for serious chronic diseases.

This news follows the 25 March 2024 announcement by Novo Nordisk of its acquisition of Cardior Pharmaceuticals for (up to) € 1.025B.

On 10 April 2024, as a result of a settlement between the parties, the US District Court for the District of New Jersey dismissed all patent infringement claims in the proceeding brought by Genentech, Hoffmann-La Roche and Biogen against Dr Reddy’s Laboratories and Fresenius Kabi in respect of Dr Reddy’s proposed DRL_RI (rituximab), biosimilar to Genentech’s/Biogen’s Rituxan®.  The terms of the settlement between the parties have not been publicly disclosed.

The proceeding was commenced on 17 November 2023, following Dr Reddy’s submission of its aBLA to the FDA seeking approval for DRL_RI.  DRL_RI was to be commercialised by Fresenius in the US and by Dr Reddy’s in other jurisdictions.

Rituximab is an old molecule and was one of the first mAbs to become “biosimilar”, with the first rituximab approval in the US on 26 November 1997. There are three rituximab biosimilars currently on the US market: Teva and Celltrion’s Truxima® (launched in May 2020),  Pfizer’s Rituxience® (launched in January 2020) and Amgen and Allergan’s Riabni^TM (approved by the FDA in December 2020).