BioBlast®

PTAB instituted Celltrion’s IPR challenges to US 10,888,601 (decision here) and US 10,130,681 (decision here) and Samsung Bioepis’ IPR challenge to US 10,888,601 (decision here).  PTAB also granted Celltrion and Samsung Bioepis’ motions to join these IPRs with the earlier IPRs filed against the same Regeneron patents by Mylan in July 2022 which were instituted in January 2023.  Celltrion and Samsung Bioepis sought to join the Mylan IPRs in February 2023.

Note:

• The ‘601 and ‘681 patents are included in the Regeneron suit against Mylan in West Virginia, filed in August 2022, and the ‘601 patent is one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.
• In January 2023, Celltrion filed a fourth IPR challenge to 10,464,992, which is yet to be instituted.
• Institution of Mylan’s challenge to 10,857,205 was recently denied after Regeneron disclaimed all claims of the patent.
• In 2022, PTAB invalidated Regeneron’s 9,254,338 and 9,669,069 for anticipation based on Mylan’s application for IPR.
• Earlier this month PTAB denied institution of the IPR filed by Apotexagainst Regeneron’s 11,253,572 patent relating to a method of treating an angiogenic eye disorder by administering a VEGF antagonist, including Eylea® (aflibercept).

Luye Pharma Group announced that it has completed patient enrolment in Ph III trials of BA9101 (also known as OT-702), biosimilar to Regeneron’s aflibercept/Eylea®.  BA9101 was developed by Luye Pharma’s subsidiary Boan Biotech with clinical studies being conducted in conjunction with Boan’s partner Ocumension Therapeutics under an agreement announced in October 2020.

PTAB denied institution of the IPR filed by Apotex against Regeneron’s 11,253,572 patent relating to a method of treating an angiogenic eye disorder by administering a VEGF antagonist, including Eylea® (aflibercept).  Apotex filed the IPR in September 2022, challenging claims 1-5, 8-11, 14 and 26 for anticipation and 6, 7, 12 and 13 for obviousness.  PTAB found that Apotex had not demonstrated a reasonable likelihood that it would prevail in showing that any of the challenged claims of the ‘572 patent is unpatentable.

The ‘572 patent is one of the 24 patents included in the Regeneron suit against Mylan in West Virginia, filed in August 2022, and one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.  No other application for IPR has been filed to date against the ‘572 patent, although there are currently 7 other applications against 3 patents pending: 10,130,681 (filed by Mylan, Celltrion and Samsung Bioepis), 10,888,601 (filed by Mylan, Celltrion and Samsung Bioepis) and 10,464,992 (filed by Celltrion).  Institution of Mylan’s challenge to 10,857,205 was recently denied after Regeneron disclaimed all claims of the patent. Last year PTAB invalidated Regeneron’s 9,254,338 and 9,669,069 for anticipation based on Mylan’s application for IPR.

In December 2022, we reported on Ontario’s biosimilar switching program which required patients to be transitioned to biosimilars (including infliximab) by 29 December 2023.

PTAB denied institution of Mylan’s IPR challenge to US10,857,205 (relating to Regeneron’s Eylea® aflibercept), after Regeneron filed a disclaimer with the USPTO, disclaiming all claims of the patent.   

–

Celltrion filed an application for inter-partes review (IPR) against a fourth Regeneron US patent 10,406,226 relating to a method of making a VEGF antagonist fusion protein, including the fusion protein aflibercept supplied by Regeneron as Eylea®.    

Celltrion previously filed IPRs against Regeneron’s method of treatment patents 10,888,601 and 10,130,681 patents on 10 February 2023, as did Viatris (Mylan) on 11 January 2023 and Samsung Bioepis on 10 February 2023 and 6 January 2023 respectively.  Last month Celltrion and Samsung Bioepis separately sought joinder of their challenges to Regeneron’s ’601 and ’681 patents with Viatris’ IPR against the ‘601 and ‘681 patents, which were instituted in January 2023.  

The Regeneron suit against Mylan in West Virginia, filed in August 2022, includes each of the ‘601, ‘681 and ‘226 patents.  The ‘601 patent is one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.  

–

Regeneron announced that the FDA has accepted for priority review its BLA for aflibercept 8mg for treatment of patients with wet age-related macular degeneration, diabetic macular edema and diabetic retinopathy.  The BLA was supported by two pivotal trials demonstrating non-inferior vision gains to EYLEA® (aflibercept) Injection, with vast majority of patients maintaining extended dosing regimens through 48 weeks.  The FDA target action date is 27 June 2023. Aflibercept 8mg is being jointly developed by Regeneron and Bayer A.G.

South Korea’s Alteogen announced that its subsidiary Altos Biologics has completed patient enrolment in its Ph III trials of ALT-L9 aflibercept (biosimilar to Regeneron’s Eylea®) in patients with neovascular  age-related macular degeneration.  Alteogen reported that it plans to submit the BLA in early 2024, with a European launch anticipated in the first half of 2025.

Celltrion and Samsung Bioepis each filed motions seeking joinder of their respective IPR challenges to Regeneron’s 10,888,601 and 10,130,681 patents for Eylea® (aflibercept) with Mylan’s, which was instituted in January 2023.

PTAB also instituted Mylan’s IPR against Regeneron’s US10,130,681.   A third Mylan IPR challenge against US10,857,205 remains pending and is likely to be initiated in April 2023.

Separately, Regeneron sued Mylan in West Virginia in August 2022, alleging infringement of 24 patents relating to Eylea (including the ‘601 patent), and a 10 day trial has been set down for June 2023, which is 10 months after Regeneron filed its complaint.

Samsung Bioepis filed a petition for inter partes review of Regeneron’s US 10,888,601, relating to Eylea® (aflibercept).  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the‘601 patent.

Regeneron announced that the FDA has approved Eylea® (aflibercept) for the treatment of preterm infants with retinopathy of prematurity.  Eylea is now approved in the US to treat five retinal conditions caused by ocular angiogenesis.

PTAB instituted two IPR petitions filed by Mylan challenging Regeneron’s US10,130,681 and US10,888,601 patents, which relate to Eylea® (aflibercept).  PTAB found that Mylan demonstrated a reasonable likelihood that at least claim 1 of the ‘681 patent and claim 34 of the ‘601 patent is unpatentable as being anticipated by the same piece of prior art.  A third Mylan IPR challenge, to Regeneron’s US10,857,205 is likely to be initiated in April 2023.

Celltrion filed a petition for inter partes review of Regeneron’s US 10,464,992, relating to Eylea® (aflibercept).  Celltrion has alleged the 992 patent is invalid on obviousness and anticipation grounds.  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the 992 patent.

Mylan filed a petition for inter partes review of Regeneron’s US 10,130,681 and US 10,888,601, relating to Eylea® (aflibercept).  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the ‘681 and ‘601 patents.

Samsung Bioepis filed a petition for inter partes review of Regeneron’s US10,130,681, relating to Eylea® (aflibercept).  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the ‘681 patent.

In its aflibercept suit against Mylan in the Northern District of West Virginia Regeneron filed an expedited motion seeking to compel Mylan  to  redesignate its biosimilar regulatory file and regulator correspondence from “Outside Counsel’s Eyes Only” (“OCEO”) to enable Regeneron’s in-house Counsel to access the materials.    Regeneron has asked the court to de-designate Mylan’s aBLA immediately to confidential, and to correct the remainder of its designations.  Regeneron asserts that its in-house Counsel has already seen a substantial portion of the materials in the patent dance.

PTAB issued decisions in Mylan’s IPR challenges relating to Regeneron’s 9,254,338 and 9,669,069 relating to Eylea® (aflibercept),  invalidating all claims the subject of the Mylan challenge, for anticipation.  Mylan’s IPRs were heard by PTAB in August 2022.  Regeneron filed a complaint against Mylan in West Virginia on 03 August 2022, alleging infringement of twenty-four patents – including the 2 subject patents – relating to Eylea® (aflibercept).

A trial date of 12 – 23 June 2023 has been set in the Regeneron v Mylan aflibercept District Court (NDWV) BPCIA dispute.  Regeneron has identified 6 patents (10,888,601, 11,053,280, 11,084,865, 11,104,715, 11,253,572 and 11,299,532) from 3 patent families for initial proceedings, and has stipulated that it will not seek injunctive relief on the other 18 patents asserted in its complaint.  This hearing date will be a mere ten months after Regeneron filed a complaint against Mylan in August 2022. Mylan filed it’s a-BLA for biosimilar aflibercept in October 2021, and received FDA notification that the application was accepted on 28 December 2021.

Regeneron announced that the FDA has granted paediatric exclusivity for Eylea® (aflibercept), extending market exclusivity in the US to 17 May 2024. Paediatric exclusivity was granted on the basis of Ph III trials of Eylea as a treatment for retinopathy of prematurity in preterm infants.

Regeneron announced that the FDA has accepted for Priority Review the sBLA for Eylea® (aflibercept) to treat retinopathy of prematurity in preterm infants.   The target action date for the FDA decision is 11 February 2023.

India’s Central Drug Standard Control Organisation granted permission to IQVIA to conduct Ph III clinical trials of Alvotech’s AVT06 (biosimilar aflibercept) for the treatment of retinal vascular diseases.

Korea Biomedical Review reported that Samsung Bioepis will present on three scientific abstracts on its ophthalmology biosimilars, aflibercept and ranibizumab, at the American Academy of Ophthalmology 2022 between 30 September – 03 October.  Samsung Bioepis reported that interim analysis of SB15 (biosimilar aflibercept) indicated an equivalence in efficacy of SB15 and Eylea® in terms of best-corrected visual acuity at 8 weeks in patients with neovascular age-related macular degeneration. This is the first time that Samsung Bioepis has disclosed data on its aflibercept biosimilar.

Apotex filed an IPR against Regeneron, seeking revocation of Regeneron’s method of treatment (MOT) patent US 11,253,572, relating to the sequential administration of 2mg doses of aflibercept (Eylea®) on the grounds of anticipation and obviousness.

Regeneron announced that the primary endpoints were met in two pivotal trials evaluating aflibercept 8mg with 12 and 16 week dosing regimes in diabetic macular edema and wet age-related macular degeneration.

Lupin and DKSH announced that they have signed an exclusive licensing and supply agreement to market five of Alvotech’s biosimilar products in the Philippines.  The biosimilars include AVT03 (biosimilar denosumab – Prolia® and Xgeva®), AVT05 (biosimilar golimumab/Simponi®) and AVT06 (biosimilar aflibercept/Eylea®) as well as two undisclosed proposed biosimilars for immunology and oncology.

The IPRs (inter-partes reviews) commenced by Mylan against Regeneron’s Eylea® patents 9,669,069 and 9,254,338 (instituted in December 2021) were heard by the PTAB together on 10 August 2022.  The patents relate to Regeneron’s blockbuster product Eylea® (aflibercept) and analysts have reported that (at least) the ‘338 patent is likely to be invalidated, based on comments made by the PTAB during the proceedings.

Regeneron has filed a complaint against Mylan in West Virginia under the BPCIA alleging infringement of twenty-four patents relating to Eylea® (aflibercept).  This follows the FDA’s acceptance for review of Mylan’s aBLA for its aflibercept biosimilar.  Regeneron recently listed twenty-nine patents in the Purple Book as part of its patent dance with Mylan.  Mylan previously sought IPR of several aflibercept patents.

Alvotech announced the initiation of its ALVOEYE clinical trials for AVT06, biosimilar to Eylea® (aflibercept) which is indicated for the treatment of adult patients with neovascular (wet) age-related macular degeneration (AMD).  AVT06 is the third Alvotech biosimilar product to enter the clinic, and is one of eight products under development.

Alvotech’s portfolio also includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar to Stelara®) for which Alvotech recently announced positive topline results; denosumab/biosimilar to Prolia®, golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.

Regeneron announced that the FDA has accepted for review the sBLA for Eylea® (aflibercept) for a 16-week 2mg dosing regimen (after initial monthly doses) in patients with diabetic retinopathy.  The FDA has set a target action date of 28 February 2023.

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.

Alvotech and Oaktree Acquisition Corp. II announced that they have entered into a merger agreement for the creation of a publicly-traded global biopharmaceutical company. Alvotech is led by a team of highly experienced biopharma leaders, including Mark Levick as CEO, Anil Okay as CCO, and Philip Caramanica as Chief IP Counsel and Deputy General Counsel. The merger is expected to deliver gross proceeds to Alvotech in excess of USD$450 million.  Alvotech currently has seven products in its pipeline, including a biosimilar candidate to Humira® (adalimumab), Stelara® (ustekinumab), Eylea® (aflibercept), Prolia®/Xgeva® (denosumab) and Simponi®/Simponi ARIA® (golimumab).

Celltrion announced its Q3 2021 financial results. Celltrion reported that Remsima® (infliximab biosimilar) has obtained a 53% market share in Europe and 21% market share in Japan. Celltrion reported that Truxima® (rituximab biosimilar) has obtained a 40% market share in Europe and Herzuma® (trastuzumab biosimilar) has obtained a 14% market share in Europe. Celltrion also reported that it expects to launch biosimilar bevacizumab in 2022, biosimilar ustekinumab in 2023, biosimilar omalizumab and aflibercept in 2024 and biosimilar denosumab in 2025.

Novartis announced the results of its Ph III trials of Beovu® (brolucizumab) versus aflibercept in patients with diabetic macular edema, reporting that Beovu® demonstrated superiority versus aflibercept in key endpoints.

Celltrion released its Q1 2020 financial results, reporting that YoY sales of Celltrion biosimilars increased by 23%.  Celltrion announced that it is planning to complete Ph III trials of biosimilar bevacizumab in the first half of 2021, and that ustekinumab, aflibercept, omalizumab and denosumab candidates remain in Ph III trials.

Sandoz announced it will commence enrolling patients in MYLIGHT, its Ph III efficacy and safety study of its proposed aflibercept biosimilar.  MYLIGHT will assess the efficacy and safety of the biosimilar candidate in comparison to Eylea® in patients with neovascular age-related macular degeneration.

Alteogen announced it has completed Ph I trials of its proposed aflibercept biosimilar ALT-L9. Alteogen reported that the trial confirmed the safety and efficacy of ALT-L9 were similar to that of Eylea®.

Korea Biomedical Review reported that Alteogen has completed Ph I trials of ALT-L9 (proposed aflibercept biosimilar).

Cipla and Alvotech announced that they have expanded their partnership for the marketing and distribution of four biosimilar medicines in Australia and New Zealand. The agreement includes biosimilar aflibercept, ustekinumab, denosumab and golimumab candidates. This agreement is in addition to the previous agreement between Alvotech and Cipla for the commercialisation of AVT02 (biosimilar adalimumab candidate).

Roche announced new Ph III data shows faricimab (given at intervals of up to four months) is non-inferior compared to aflibercept (given every two months). This may reduce the treatment burden for patients suffering from diabetic macular edema and neovascular age-related macular degeneration.

Celltrion announces it has commenced Ph III trials of its proposed aflibercept biosimilar.

Ocumension Therapeutics announces it has reached an agreement with Shandong Boan Biological Technology to jointly develop OT-702, a proposed aflibercept biosimilar. Under the agreement, Ocumension has been granted an exclusive license to promote and commercialise the product in mainland China. OT-702 is currently in Ph III trials.

Samsung Bioepis announces it has commenced Ph III trials of SB15, proposed aflibercept biosimilar.

Samsung Bioepis announces it has received approval to commence a global Ph III trial of SB15 (proposed aflibercept biosimilar) in patients with age-related macular degeneration.

JD Supra reports on Mylan’s Q1 earnings call. In the call, Mylan announced that the BLA and marketing authorisation for its bevacizumab candidate is currently under review by the FDA and European authorities. Mylan also confirmed that its biosimilar insulin and aflibercept projects remain on target.

Formycon releases an update on its biosimilar portfolio, announcing its biosimilar aflibercept candidate is proceeding as expected, with Ph III clinical trials expected to begin mid-2020.

Biogen and Samsung Bioepis announce partnership for the commercialisation of biosimilars ranibizumab and aflibercept. The agreement covers the US, Canada, Europe, Japan and Australia. Under the agreement, Biogen will make one $100M upfront payment, with up to $210M payable at additional development, regulatory and sales-based milestones.

Gene Techno Science and Kishi Kasei announce agreement for the joint development of an aflibercept biosimilar.

Alteogen announces Phase I clinical trials of biosimilar aflibercept candidate will begin this month.

Regeneron announces FDA approval for Eylea® in 2mg, single dose prefilled syringe. The product is expected to launch this year and will require fewer preparation steps in comparison to the previously approved vials.

Alteogen announces new drug application to the Ministry of Food and Drug Safety for aflibercept biosimilar, ALT-L9.

Regeneron announces $4.07 billion in 2018 US net sales for Eylea®, as it awaits the commencement of new clinical trials for a high dose formulation.  Additionally, the FDA has assigned 13 May 19 as the action date for a potential new indication in diabetic retinopathy.

Alteogen announces it has been granted a process patent for producing aflibercept biosimilar, ALT-L9.  Alteogen reports the process improves the productivity and quality of large-scale production of fusion proteins.

Regeneron announces completion of Phase III clinical trials of Eylea® (aflibercept) in patients with moderately severe and severe non-proliferative diabetic retinopathy.  The company reported the trial met its one year primary endpoint and key secondary endpoints.

Momenta announces a shift in focus from biosimilars to novel therapeutics. The 5 year re-structuring plan will involve cuts to staff of 50%, however the company will continue to develop biosimilar aflibercept candidate M710.

Coherus BioSciences discloses that preclinical studies will be ongoing in 2018 for CHS-2020 biosimilar aflibercept.

Korean Biosimilar company Alteogen announces completion of pre-clinical studies relating to ALT-L9, biosimilar aflibercept, and that it intends to file an investigational NDA with the US in 2018.  It also intends to roll out aflibercept in Japan (through partner Kissei Pharmaceutical) and China in 2022 “when the patents of the brand-name drug lapse”.

Mylan and Momenta announce deal relating to the development of M710, biosimilar aflibercept.  Pivotal clinical trials are planned for early 2018.