PIGF

FDA signage at its office in Maryland iStock, hapabapa The regulator on Monday approved two interchangeable biosimilars to Regeneron’s Eylea, providing additional competition for the pharma’s blockbuster as key patent protections are set to expire. The FDA on Monday approved two biosimilars to Regeneron Pharmaceuticals ’ blockbuster eye injection Eylea (aflibercept)—Biocon Biologics’ Yesafili (aflibercept-jbvf) and Samsung Bioepis and Biogen ’s Opuviz (aflibercept-yszy). Yesafili and Opuviz also have the FDA’s interchangeability designation, which means they may be used in place of the reference branded product without needing to consult the prescriber, according to the FDA’s announcement. It is not yet clear when the two biosimilars will launch in the U.S. and what their list prices will be, though Biocon has announced that Yesafili will be available in Canada no later than July 1, 2025 , under a settlement agreement. Like the reference product, Yesafili and Opuviz are designed to be administered via an intravitreal injection and are indicated for wet age-related macular degeneration, macular edema following retinal vein occlusion, diabetic retinopathy and diabetic macular edema. Monday’s approval follows the FDA’s comprehensive review of data showing that Yesafili and Opuviz are “highly similar to Eylea” and that the biosimilars show “no clinically meaningful differences.” These data include physicochemical and biological tests, which confirmed that the biosimilars were structurally and functionally similar to Eylea, according to the regulator. The FDA also reviewed comparative clinical data, showing that the biosimilars did not differ from Eylea in terms of efficacy, safety and immunogenicity. The reference product Eylea is a soluble decoy receptor that binds both the VEGF-A and PIGF ligands, preventing them from activating their corresponding receptors. This mechanism of action allows Eylea to prevent the abnormal growth of blood vessels in the eyes. While Eylea is exclusively commercialized by Regeneron in the U.S., it is partnered with Bayer outside the country with profits shared equally between the companies. The drug was first approved by the FDA in 2011 for the treatment of wet age-related macular degeneration. Since then, it has won several other indications and has become one of Regeneron’s best-performing assets. In 2021, the eye injection brought in $9.2 billion worldwide , increasing to $9.6 billion the following year. However, in 2023, Eylea sales slipped to nearly $9.4 billion primarily due to strong competition from Roche’s Vabysmo (faricimab-svoa). Key patent protections for Eylea are set to expire this year and Regeneron has been fending off would-be competitors with a spate of lawsuits. In December 2023, it won a case against Viatris keeping the biotech’s biosimilar out of the U.S. until 2027. Regeneron also has a case against Samsung Biologics . Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

Pictured: FDA signage at its office in Maryland/iStock, hapabapa The FDA on Monday approved two biosimilars to Regeneron Pharmaceuticals’ blockbuster eye injection Eylea (aflibercept)—Biocon Biologics’ Yesafili (aflibercept-jbvf) and Samsung Bioepis and Biogen’s Opuviz (aflibercept-yszy). Yesafili and Opuviz also have the FDA’s interchangeability designation, which means they may be used in place of the reference branded product without needing to consult the prescriber, according to the FDA’s announcement. It is not yet clear when the two biosimilars will launch in the U.S. and what their list prices will be, though Biocon has announced that Yesafili will be available in Canada no later than July 1, 2025, under a settlement agreement. Like the reference product, Yesafili and Opuviz are designed to be administered via an intravitreal injection and are indicated for wet age-related macular degeneration, macular edema following retinal vein occlusion, diabetic retinopathy and diabetic macular edema. Monday’s approval follows the FDA’s comprehensive review of data showing that Yesafili and Opuviz are “highly similar to Eylea” and that the biosimilars show “no clinically meaningful differences.” These data include physicochemical and biological tests, which confirmed that the biosimilars were structurally and functionally similar to Eylea, according to the regulator. The FDA also reviewed comparative clinical data, showing that the biosimilars did not differ from Eylea in terms of efficacy, safety and immunogenicity. The reference product Eylea is a soluble decoy receptor that binds both the VEGF-A and PIGF ligands, preventing them from activating their corresponding receptors. This mechanism of action allows Eylea to prevent the abnormal growth of blood vessels in the eyes. While Eylea is exclusively commercialized by Regeneron in the U.S., it is partnered with Bayer outside the country with profits shared equally between the companies. The drug was first approved by the FDA in 2011 for the treatment of wet age-related macular degeneration. Since then, it has won several other indications and has become one of Regeneron’s best-performing assets. In 2021, the eye injection brought in $9.2 billion worldwide, increasing to $9.6 billion the following year. However, in 2023, Eylea sales slipped to nearly $9.4 billion primarily due to strong competition from Roche’s Vabysmo (faricimab-svoa). Key patent protections for Eylea are set to expire this year and Regeneron has been fending off would-be competitors with a spate of lawsuits. In December 2023, it won a case against Viatris keeping the biotech’s biosimilar out of the U.S. until 2027. Regeneron also has a case against Samsung Biologics. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Pictured: Healthcare worker conducting an eye exam on a female patient/iStock, peakSTOCK 4D Molecular Therapeutics on Saturday unveiled topline results from its Phase II PRISM study, showing that its investigational gene therapy 4D-150 can significantly ease treatment burden in patients with wet age-related macular degeneration. Over 24 weeks of follow-up, 84% of patients treated with 4D-150’s higher 3E10-vg/eye dose did not need supplemental injections with Regeneron and Bayer’s Eylea (aflibercept), a cornerstone anti-VEGF therapy for wet age-related macular degeneration (AMD). At the lower dose group of 1E10 vg/eye, only one patient needed supplemental Eylea. Also, 63% and 50% of patients in the high- and low-dose groups, respectively, did not need supporting Eylea treatment. Overall, the high dose level of 4D-150 reduced annual Eylea injections by 89%, while the lower dose cut Eylea rates by 85%. In terms of safety, PRISM found no instance of significant inflammation, even in the high-dose group. In addition, 97% of treated patients completed their 20-week prophylactic topical corticosteroid taper according to schedule, while none of the patients were on steroids at the time of data collection. 4DMT reported these data at the Angiogenesis, Exudation, and Degeneration 2024 Conference, held virtually on Friday. CEO David Kirn said in a statement that the company is “thrilled” about these data, which “strongly validate 4D-150’s potential as a safe, convenient, durable and transformational intravitreal therapeutic for wet AMD patients, with a goal of preserving vision for the longer term.” “We believe 4D-150 has the potential to disrupt the current treatment paradigm in these patients,” Kirn added. 4D-150 is an investigational gene therapy that delivers a transgene cassette that expresses both aflibercept and an RNA interference molecule that blocks the VEGF-C protein. The double-payload approach allows 4D-150 to inhibit four VEGF family members—VEGF A, B, C and PIGF—which are central to the pathology of wet AMD and diabetic macular edema. The investigational gene therapy also uses 4DMT’s proprietary R100 vector, which enables its single, low-dose intravitreal delivery that avoids significant inflammation. 4DMT is planning to take 4D-150 into late-stage studies based on ongoing talks with the FDA and European Medicines Agency. The first Phase III study, which is set to launch in the first quarter of 2025, will be a non-inferiority study versus Eylea using the higher dose of 4D-150. In the latter half of 2024, the company is expecting interim 24-week landmark data analysis from PRISM’s population extension cohort, which is looking at 4D-150 in a patient population with broader disease severity. 4DMT is also trialing the gene therapy in diabetic macular edema, for which it is running the Phase II SPECTRA study. Initial data and analysis are also expected in the latter half of 2024. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.