Even though the subretinal gene therapy AVA-101 met its primary endpoint of maintaining visual acuity with fewer anti-VEGF injections, the results from a phase 2b study were mixed.
Mean change in retinal thickness from baseline increased 25 mm in treated patients while controls experienced a 56 mm reduction in retinal thickness. Additionally, while treated patients gained 2.2 letters of BCVA from baseline, control patients’ vision dropped 9.3 letters, suggesting the possibility that the improved vision was not due to a therapeutic effect, but an imbalance between the study and control groups.
News of the top-line data and several analyst downgrades caused the company’s stock to fall more than 50% on Tuesday.
Avalanche Biotechnologies is developing AVA-101 as a single subretinal injection to treat wet AMD for a longer duration, reducing the need for frequent injections. AVA-101 contains the AAV2 vector and a gene encoding sFlt-1, a naturally-occurring anti-VEGF protein. When administered in the eye and expressed by the host retinal cells, the sFlt-1 protein inhibits the formation of new blood vessels and reduces vascular permeability by binding and blocking VEGF activity. In this interview from ASRS 2014, Dr. Jeffrey S. Heier further describes the treatment.
The Phase 2a study randomized 32 subjects age 55 or older to receive AVA-101 plus ranibizumab (21 patients) or ranibizumab alone (11 patients). 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.
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.
BCVA improved at least 10 letters with 2 or fewer rescue injections in 23.8% of the treated group, while no patient in the control group achieved those results.
"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 Avalanche Chief Medical Officer Samuel B. Barone, MD, in a press release.
The company plans to initiate the phase 2b study later this year, the release said.