Following up on our previous post on looming biosimilar approvals over Eylea®(Aflibercept), on March 4, Biocon Biologics Limited (BBL), a subsidiary of Biocon Limited, announced that it has signed a settlement agreement with EYLEA®’s originators – Bayer Inc. and Regeneron pharmaceuticals Inc. regarding YESAFILI® – Biocon Biologics’ proposed biosimilar to EYLEA® and has been able to secure a market entry date in Canada which is no later than July 1^st, 2025. This settlement sets right multiple parallel patent infringement proceedings in the Federal Court of Canada involving several use and formulation patents (Table 1) and associated judicial review proceedings under Canada’s patented medicines (Notice of compliance) regulations addressing pre-entry pharmaceutical patent litigation.

In March 2023, Health Canada granted tentative approval for YESAFILI® 2 mg vials, subject to conclusion of any patent disputes. YESAFILI® had also received marketing authorization in the European Union by the European Commission in September 2023 which was followed by the marketing authorization in the UK by Medicines and Healthcare products Regulatory Agency (MHRA) in November 2023.

YESAFILI®, a VEGF inhibitor, is used for the treatment of various eye conditions including age related macular degeneration (AMD), diabetic macular edema (DME), macular edema secondary to retinal vein occlusion (RVO) and myopic chordal neovascularization (myopic CNV). It works by inhibiting vascular endothelial growth factor (VEGF), a protein that plays a key role in the formation of abnormal blood vessels in the eye thereby reducing abnormal vessel growth and leakage which are characteristic features of various retinal diseases. Like EYLEA®, YESAFILI® is administered via intravitreal injection directly into the eye. It is developed to provide a more affordable treatment option while maintaining comparable efficacy and safety to its reference product, EYLEA®.

According to estimates, 200 million people worldwide are suffering from AMD and by 2040 this number is projected to get close to 300 million. Due to its chronic character, which necessitates steady long-term management, AMD has become and will continue to be a public health concern for both HICs and LMICs with considerable socio-economic consequences and surge in healthcare costs. It is also the leading cause of blindness in people over the age of 55, affecting close to 2.5 million Canadians, with nearly 1,80,000 people experiencing vision loss. Given Canada’s aging population, these numbers will continue to grow.

There have been some retinal diseases treatment programs in Canada which cover the cost of the monthly injections that are required for such kind of diseases but there has been an announcement that specialists might intend to withdraw from the treatment programs as with inflation, the rising costs of facilities, equipment supplies, and staffing, it is simply not sustainable to continue to participate in the programs making it difficult for the patients to pay upfront for the treatment which costs about $1700 per visit and then seek reimbursement from the province. Some patients are unlikely to be able to afford these costs and are preparing for the loss of vision in one of their eyes if there is no resolution for it. The cost of Aflibercept is in the range of $6,092 to $20,887 in Canada and the entry of the biosimilar, YESAFILI® in 2025 would indeed be a big relief for the patients, making it affordable for them.

Eylea’s competitor in the Canadian market, Roche’s Vabysmo®, has two therapeutic targets, VEGF-A and Angiopoietin 2. It gained the status of blockbuster drug in 2023 within a span of 19 months from its launch in the market. It shows a good safety profile with very low rates of inflammation. The most significant advantage of Vabysmo® over Eylea® was the potentially reduced frequency of treatment but Regeneron had come up with an 8 mg version of EYLEA® whose trials suggest superior staying power and now EYLEA®’s biosimilar entry YESAFILI® has further given an undue advantage to it as there are currently no biosimilars in pipeline for Vabysmo®. The Canadian patent CA2527618 for Vabysmo® is set to expire in July 2035.