Investors Move Fast on AERI, AAVL Clinical News

Investors Move Fast on AERI, AAVL Clinical News
Two presenters at the OIS saw their stock prices shoot in different directions following the release of news related to late-stage clinical trials.

On Tuesday, Aerie Pharmaceuticals, received approval from the Food and Drug Administration to change the primary endpoint of its second Phase 3 trial of Rhopressa, its rho kinase (ROCK) inhibitor for reduction of intraocular pressure (IOP) in glaucoma.

The trial, known as Rocket 2, will now have a primary endpoint range to include patients with baseline IOPs in the 20–25 mm Hg range, the same range where the Phase 3 registration trial results of Rocket 1 had shown success. The former range for the primary endpoint in Rocket 2 was 20–27 mm Hg, which will now represent a secondary endpoint range.

The release of the news drove up Aerie’s shares by more than 50%, restoring the value lost in April when the company released early Phase 3 results showing its Rhopressa one-day eyedrop for lowering intraocular pressure failed to meet its primary endpoint of showing comparable efficacy to twice-daily timolol.

Meanwhile, Avalanche Biotechnologies’ stock took a plunge similar to Aerie’s April dive, dropping more than 56% a day after the company announced what it called “positive” topline results of a single-center, open-label Phase 2a trial of its AVA-101 gene therapy for wet age-related macular degeneration (AMD). Analysts, however, weren’t so positive; three downgraded their recommendations after the announcement.

The analysts cited concerns about a finding in the Phase 2a results that showed increases in retinal thickness and modest overall vision gain from baseline in the treatment group.

Investors sold more than 660,000 shares of Avalanche stock the day of the announcement and more than 2.1 million shares the next day, compared to the previous 52-week one-day high of almost 500,000 shares in January this year. The stock price tumbled from around $40 a share to near its $17 IPO price.

The Phase 2a study involved 32 subjects age 55 or older with wet AMD. Twenty-nine of 32 subjects had received prior anti-VEGF therapy, with a median of 10 prior injections. In the study, all subjects received two Lucentis (ranibizumab, Genentech) injections at day 0 and week 4, and all were permitted to receive Lucentis rescue therapy beginning at week 8. Twenty-one subjects were randomized to the AVA-101 treatment group, 11 to the control group.

The study’s primary endpoint was safety, while secondary endpoints included mean change from baseline in best-corrected visual acuity (BCVA), the number of Lucentis rescue injections and mean change in central retinal thickness from baseline as measured by spectral-domain optical coherence tomography (SD-OCT). All subjects remained in the study through the 12-month study term.

On the primary endpoint, no subjects showed serious adverse events, and all adverse events related to the drug were mild or moderate and resolved within 60 days.

Drilling down into the study data, the treatment group showed a 2.2-letter gain in BCVA from baseline compared to a 9.3-letter loss among controls. About a quarter (23.8%) of the treatment group gained 10 letters or more with two or fewer rescue injections.

The AVA-101 treatment group also had fewer rescue injections, a median of two compared with four among controls. Nineteen percent of subjects in the treatment group required no retreatments vs. 9.1% in the control group.

In a conference call with Avalanche executives, analysts raised questions about study results that showed a mean increase in retinal thickness of 25 microns in treated subjects compared with a decrease of 56 microns in controls, which one analyst said seemed to be counter to improvement in BCVA. Company executives told analysts the findings on retinal thickness were “not well correlated,” but the individual patient data has not yet been analyzed. They said the company would use outside imaging consultants to better understand the data.

Nonetheless, Avalanche CEO Thomas Chalberg said that the Phase 2a findings would help inform a multicenter Phase 2b trial in the United States later this year.