Avalanche Biotechnologies, Inc. Announces Positive Top-Line Phase 2a Results for AVA-101 in Wet Age-Related Macular Degeneration

Avalanche Biotechnologies, Inc. AAVL today announced that its Phase 2a clinical study for AVA-101 met its 12-month primary endpoint, based on ophthalmic and systemic safety, demonstrating that AVA-101 was well tolerated with a favorable safety profile in subjects with wet age-related macular degeneration (wet AMD). AVA-101 also showed an improvement on best corrected visual acuity (BCVA) compared with the control group and a positive trend in response rate (stable vision with few rescue injections). AVA-101 is being developed as a sub-retinal gene therapy injection to provide a safe and effective treatment for wet AMD that is durable and reduces the need for frequent anti-VEGF injections. "The results of this study confirm the Phase 1 safety results and suggest that AVA-101 could potentially benefit a significant portion of patients with wet AMD who require regular treatment with anti-VEGF therapy," said Samuel B. Barone, M.D., Avalanche's chief medical officer. "The current standard of care in wet AMD requires frequent anti-VEGF injections, which present a significant burden for patients and their caregivers, and can result in reduced treatment compliance and under-treatment. Therefore, a product that can maintain or improve vision while reducing the number of treatment injections would represent a powerful new option for patients and physicians." In the study, BCVA mean change from baseline showed a difference of 11.5 letters between the treatment (+2.2 letters) and control (-9.3 letters) groups (95 percent CI, 2.3-20.7 letters). Additionally, a significant number of AVA-101 treated subjects (42.9 percent) improved or maintained stable vision with two or fewer rescue injections compared with subjects in the control group (9.1 percent). Importantly, BCVA improvement of at least 10 letters with two or fewer rescue injections was observed in 23.8 percent of treated subjects and 0 percent of subjects in the control group. "AVA-101 demonstrated tolerability and a promising treatment effect in the subjects treated in this study, many of whom had been extensively treated with anti-VEGF therapy prior to enrollment and showed difficult-to-treat characteristics including persistent recurrent wet AMD activity," said Thomas W. Chalberg, Jr., Ph.D., Avalanche's co-founder and chief executive officer. "These data will help inform our future study designs, including the Phase 2b study that we plan to initiate later this year. We believe AVA-101 has the potential to substantially improve the standard of care and lower the high burden of treatment for patients suffering from wet AMD." The Phase 2a study enrolled 32 subjects age 55 or older with wet AMD and randomized them to an AVA-101 treatment group (n=21) or a control group (n=11). Subjects in both groups received two ranibizumab injections at day 0 and week 4, and ranibizumab rescue therapy was allowed according to pre-specified criteria beginning at week 8. Twenty-nine of 32 subjects had received prior anti-VEGF therapy, with a median of 10 prior injections.(1) The primary endpoint of the study was safety, as measured by ophthalmic and/or systemic complications. Secondary endpoints included mean change from baseline in BCVA, the number of ranibizumab rescue injections, and mean change from baseline in central retinal thickness as measured by SD-OCT. All subjects remained in the study through the 12-month study visit. No serious adverse events related to AVA-101 were observed. One subject in the treatment group experienced a non-fatal myocardial infarction classified as unrelated to therapy. In the control group, one case of endophthalmitis was observed. All adverse events related to study drug were mild or moderate and resolved within 60 days. There were no unexpected administration-related adverse events, and any events that occurred resolved without visual sequelae. Although the study was not designed to show statistically significant differences between the active and control subjects in the secondary endpoints, the following results were observed: Overall, BCVA mean change from baseline did show a significant difference of 11.5 letters between the treatment (+2.2 letters) and control (-9.3 letters) groups (95 percent CI, 2.3-20.7 letters). More AVA-101 treated subjects improved or maintained stable vision (>-5 letters) with a low number (≤2) of rescue treatments. Specifically, 23.8 percent (treated) vs. 9.1 percent (control) maintained stable vision with ≤ rescue injections, and a significant number of AVA-101 treated subjects (42.9 percent) improved or maintained stable vision with ≤2 rescue injections compared with subjects in the control group (9.1 percent). BCVA improvement of ≥10 letters with ≤2 rescue injections was observed in 23.8 percent of treated subjects and 0 percent of subjects in the control group. The median number of rescue injections using the protocol-specified retreatment regimen was 2 (95 percent CI, 1-6 injections) in AVA-101 treated subjects compared with 4 (95 percent CI, 3-5 injections) in the control group. More subjects required fewer retreatments in the treatment group compared with control (19.0 percent vs. 9.1 percent with 0 injections; 33.3 percent vs. 9.1 percent with ≤1 injections; 52.4 percent vs. 9.1 percent with ≤2 injections). Retinal thickness mean change from baseline, as reported by the site using automated segmentation, was +25 mm for AVA-101 treated subjects compared with -56 mm in the control group (CI for the difference, 17 to 145 mm). Additional evaluation of SD-OCT images by an image reading center are ongoing. Detailed data from the AVA-101 Phase 2a study will be presented at upcoming medical conferences this year. These data will help inform the design of Avalanche's Phase 2b AVA-101 study, which the Company plans to conduct at multiple centers in the United States. Phase 1 Study 36-Month Data Avalanche also announced today 36-month follow up data on eight subjects treated in the Phase 1 study of AVA-101, which confirmed the safety profile of the drug previously reported at 12 months. Long-term follow-up for subjects from the Phase 1 study included planned visits at 18 and 36 months to evaluate long-term safety. During the long-term follow up period, anti-VEGF rescue treatment was determined at the discretion of the subject's physician. Six of the eight subjects were available for evaluation at 36 months, four from the treatment group and two from the control group. Two subjects withdrew from the study for reasons unrelated to study drug. Through 36 months, AVA-101 was shown to be well tolerated with no significant drug-related safety concerns in all four subjects from the treatment group. Among the four AVA-101 treated subjects with data available through 36 months, the mean change from baseline to month 36 was +0.5 letters and subjects received an average of 0.71 rescue injections per year, after the two required ranibizumab injections. Detailed data from this long-term follow up study will be reported at a medical meeting later this year. Conference Call Today at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time) Avalanche will host a teleconference and webcast to discuss the information in this press release. The live call may be accessed by phone by calling (844) 824-7426 (domestic) or (330) 863-3278 (international), conference ID 62079488. The webcast can be accessed on the Investor Relations section of the Avalanche website at www.avalanchebiotech.com and will be archived for 14 days following the call. A replay of the call will be available by phone by calling (855) 859-2056, participant code 62079488.