麻豆传媒

The FDA has approved the first interchangeable biosimilar to the ophthalmologic anti-VEGF agent ranibizumab (Lucentis), Coherus BioSciences .

The approval of ranibizumab-eqrn (Cimerli) covers all five current FDA-approved indications for ranibizumab -- neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), diabetic retinopathy, macular edema following retinal vein occlusion, and myopic choroidal neovascularization. The biosimilar cannot, however, be used with the port delivery system developed for the reference drug.

Principal support for approval came from the randomized, multicenter, phase III involving patients with nAMD. The trial involved 477 patients, who were randomized to ranibizumab-eqrn or the reference product. Patients in both groups received a 0.5-mg intravitreal injection in the study eye every 4 weeks. The primary endpoint was change in best corrected visual acuity (BCVA) after 8 weeks, with an equivalence margin of three letters.

The primary analysis showed a mean improvement of 5.1 letters with the biosimilar and 5.6 letters with reference ranibizumab (-0.4 difference, 90% CI -1.6 to 0.9). Ocular and systemic safety profiles were similar between the treatment groups.

An email from FDA's Center for Drug Evaluation and Research noted that ranibizumab-eqrn received approval as a "biosimilar to, and interchangeable with" reference ranibizumab.

"A biosimilar is a biological product that is highly similar to an existing FDA-approved biological product, known as a reference product," the agency said. "The biosimilar must also have no clinically meaningful differences in terms of safety and effectiveness from the reference product. A biosimilar sponsor may choose to also seek an interchangeability determination by demonstrating that their product also meets specific requirements outlined in the Public Health Service Act.

"In addition to meeting the same standard for biosimilarity, additional requirements for interchangeability include a determination that the proposed interchangeable can be expected to produce the same clinical result as the reference product in any given patient; and that the risk in terms of safety or diminished efficacy of alternating or switching between the proposed interchangeable and the reference product is not greater than the risk of using the reference product without such alternation or switch," the email continued. "FDA's approval of an interchangeable biosimilar product does not indicate a higher standard of biosimilarity."

Interchangeability means that a product can be substituted for the reference product without consulting the prescriber, the FDA explained. Laws pertaining to so-called pharmacy-level substitution vary from state to state, and to date the FDA has approved only two other interchangeable biosimilars, insulin glargine-yfgn injection (Semglee) and adalimumab-adbm (Cyltezo).

Also called FYB201, the ranibizumab biosimilar was developed by Bioeq of Zug, Switzerland as a joint venture between Polpharma Biologics (with offices in Poland and the Netherlands) and Munich-based Formycon. By means of a licensing agreement, Coherus BioSciences has exclusive U.S. distribution rights for the biosimilar. The exclusivity period lasts for 12 months after market launch, which should occur by early October, according to Coherus. The biosimilar will be available in doses of 0.3 and 0.5 mg.

In September 2021, the FDA approved (Byooviz) as the first biosimilar to the reference product, but that approval did not include interchangeability.

The biosimilar market (and competition) for ocular anti-VEGF products will likely continue to expand. At the recent American Society of Retina Specialists meeting, a report from a randomized trial of a biosimilar to reference aflibercept (Eylea) demonstrated equivalence with respect to BCVA and central retinal thickness in patients with DME. Safety and immunogenicity profiles were similar between the biosimilar and reference drug.

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