- Relatively recent IPO Avalanche Biotechnologies (AAVL) craters 40% after hours on robust volume in response to its announcement of top-line results from a Phase 2a study assessing its lead product candidate, AVA-101, in patients with wet age-related macular degeneration (wet AMD). The primary endpoint of the trial was safety, but secondary efficacy measures have apparently disappointed investors despite the study not being powered to show statistical significance.
- The trial enrolled 32 wet AMD patients at least 55 years old. They were randomized to receive AVA-101 (n=21) or control (n=11). Both arms received two ranibizumab injections [Roche's (OTCQX:RHHBY) Lucentis] at day 0 and week 4. Almost all (n=29/32) had received prior anti-VEGF therapy with a median of 10 prior injections.
- The mean change in best corrected visual acuity (BCVA) from baseline in the AVA-101 cohort was +2.2 letters compared to -9.3 letters for control. In addition, 42.9% of patients (n=9/21) receiving AVA-101 improved or maintained stable vision with two or fewer rescue injections compared to 9.1% (n=1/11) for control. BCVA improvement of at least 10 letters with no more than two rescue injections occurred in 23.8% of the AVA-101 arm versus 0% in control.
- The modest average letter gain for the AVA-101 arm is substantially less than published studies of Eylea and Lucentis, which have demonstrated mean improvements in BCVA scores of 18.9 letters and 14.2 letters, respectively. If the difference persists in subsequent studies, then Regeneron will be less likely to take advantage of its right of first negotiation for the rights to AVA-101.
- The value proposition of AVA-101, a gene therapy that contains a gene that encodes a naturally occurring anti-VEGF protein, is a single subretinal injection compared intravitreal (inside the eye) injections as frequent as once per month for Regeneron's (REGN) Eylea and Roche's Lucentis.