Formycon, the German-based developer of biosimilar agents, may be getting a leg up in the race to develop biosimilars for intravitreal anti-VEGF agents as it launched the first Phase III pivotal trial of its biosimilar to Genentech’s Lucentis (ranibizumab) while also revealing details of its program to develop a biosimilar to Regeneron’s Eylea (aflibercept).
Biosimilars are to biological agents like Eylea and Lucentis what generics are to brand-name drugs, but with a caveat: the FDA approval pathway for biosimilars is not as straightforward. Since Congress passed the Biologics Price Competition and Innovation Act in 2009, the FDA has approved only one biosimilar agent, Sandoz’s Zarxio, a biosimilar to Neupogen (filgrastim), a white cell booster for patients on chemotherapy.
And where a generic drug can get approval for all indications of its reference product, a biosimilar could get approved for only one or some indications of its reference product. The rules for prescribing, substituting, and naming biosimilars are also up in the air. The FDA has come under fire for failing to finalize regulations, much to the frustration of the biopharma industry, politicians, and consumer groups who want more biosimilars to provide competition to expensive biological agents.
The Phase III study for Formycon’s FYB201 is designed to compare the agent with Lucentis in terms of safety, efficacy, and immunogenicity in neovascular AMD. Lucentis is also approved for macular edema following retinal vein occlusion (RVO) and diabetic macular edema (DME), but because of nuances in the biosimilars approval process Formycon may not get approval for all three indications when and if approval should come. The trial will enroll 650 participants in 89 centers worldwide.
In 2015, Formycon out-licensed FYB203, the Eylea biosimilar, exclusively to Santo Holding GmbH, but revealed details only a few weeks ago. Eylea has the same indications as Lucentis.
Santo subsidiary Bioeq GmbH plays a key role in both Formycon programs. Bioeq is the sponsor of the Phase III study for FYB201, and will be responsible for the clinical development, approval, and global marketing and licensing of FYB203. Both development programs are being coordinated with the FDA as well as the European Medicines Agency.
“The development of biosimilars for Lucentis and Eylea has made us pioneers in the area of ophthalmology biosimilars with the two most important products in this field,” Formycon CEO Dr. Carsten Brockmeyer says. “We believe we are the only company with a Lucentis biosimilar already in the pivotal Phase III clinical study. Our strong position is also underlined by the number of formulation and application patents we have already filed, which gives us a further competitive advantage.”
He says Formycon’s goal is to “launch our biosimilars on the market at day one after the patent on the reference product expires.”
Patents for Lucentis are due to expire in 2020 in the US and 2022 in Europe, according to information Bernstein senior analyst Ronny Gal, PhD, reported at a biosimilars conference last year. For Eylea, patents expire in 2020 and 2021 in the US and Europe, respectively, according to the journal Nature.
Formycon is not alone in the intravitreal anti-VEGF biosimilars space. San Diego-based Pfenex signed a collaboration agreement last year with Pfizer subsidiary Hospira for PF582, its Lucentis biosimilar candidate. Pfenex expects to undertake its pivotal clinical comparator trial for PF582 this year. The Pfizer collaboration netted Pfenex an up-front payment of $51 million and milestone payments valued at up to $291 million as well as tiered double-digit royalties on net sales of PF582. Pfizer is responsible for the clinical comparative trial and the companies will share the costs of the trial 50/50 up to a cap for Pfenex of $20 million, with $10 million of that offset as a credit against royalties.
Last year, Intas Pharmaceuticals in India became the first company to commercialize an intravitreal anti-VEGF biosimilar when it launched Razumab in that country.
The anti-VEGF market is lucrative for biosimilar companies. Lucentis recorded estimated sales of $3.5 billion in 2015 and Eylea more than $2.7 billion.The total market for intravitreal anti-VEGF treatments in 2015 was around $7.5 billion, according to Formycon estimates.