On July 24, Outlook Therapeutics announced that ONS-5010 (bevacizumab, brand name: Lytenava) received FDA approval for the treatment of wet age-related macular degeneration (wAMD). This is the first ophthalmic bevacizumab formulation approved by the FDA.

The original bevacizumab ( Avastin ) is an anti-VEGF-A monoclonal antibody developed by Roche and is currently only indicated for cancer patients. ONS-5010 has completed four Phase III studies to date, including NORSE ONE, NORSE TWO, NORSE THREE, and NORSE EIGHT . NORSE ONE was a proof-of-concept study that included 61 patients with wAMD. The results showed that the proportion of patients in the ONS-5010 group who achieved an increase of more than 15 letters in their best corrected visual acuity (BCVA) score was not significantly different from that in the ranibizumab group (11.8% vs. 22%).The NORSE TWO study included 228 patients with wAMD. Results showed that the proportion of patients achieving an increase of 15 or more letters in their BCVA score was significantly higher in the ONS-5010 group than in the ranibizumab group (intention-to-treat population: 41.7% vs. 23.1%, P=0.0052; adherent population: 41.0% vs. 24.7%, P=0.0409). Furthermore, in the intention-to-treat population, the ONS-5010 group showed a statistically significant increase of 11.2 letters in their BCVA score, while the ranibizumab group showed an increase of 5.8 letters (P=0.0043), consistent with the trend observed in the adherent population.The NORSE THREE study included 197 patients with wAMD, diabetic macular edema (DME), and macular edema secondary to retinal vein occlusion ( RVO) . Results showed that ONS-5010 (administered monthly) had manageable safety.

The NORSE EIGHT study included 400 newly diagnosed wAMD patients. Results showed that at week 8 of treatment, in the intention-to-treat population, there was no significant difference in the mean BCVA between the ONS-5010 (1.25 mg, every 4 weeks) group and the ranibizumab (0.5 mg) group (+4.2 vs +6.3 letters, difference -2.257, 95% CI: -4.044, -0.470; P=0.0863), failing to meet the lower limit of non-inferiority (-3.5) pre-specified by the FDA in the Special Protocol Assessment (SPA) and also failing to meet the p-value requirement (P>0.025). With extended follow-up, at week 12 of treatment, the BCVA scores in the ONS-5010 group and the ranibizumab group increased by 5.5 and 6.5 letters, respectively (P=0.0043).
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