Aldeyra Therapeutics Faces Setback in Dry Eye Disease Treatment
Aldeyra Therapeutics Inc. (ALDX) experienced a significant stock drop following the FDA's identification of substantive review issues in its New Drug Application (NDA) for reproxalap, a treatment for the signs and symptoms of dry eye disease. The FDA communicated these concerns in minutes from a late-cycle review meeting, stating that the NDA lacks sufficient data to support reproxalap's efficacy for the intended indication. The regulatory body also requested additional chemistry, manufacturing, and controls (CMC) details.
Despite Aldeyra's submission of responses aimed at mitigating the identified review issues and CMC requests, the FDA has not confirmed the sufficiency of the provided information. Instead, the FDA has suggested that Aldeyra conduct an additional clinical study to adequately address efficacy requirements. Aldeyra initially submitted its NDA for reproxalap in December 2022, and the FDA accepted it for filing in February 2023, setting a target action date of November 23, 2023. Given the FDA's concerns, approval by the target date or even afterward appears unlikely, with a Complete Response Letter (CRL) being a potential outcome.
Annovis Bio Announces Positive Interim Analysis for Buntanetap in Alzheimer's Disease
Annovis Bio Inc. (ANVS) announced positive interim results from its Alzheimer's Disease (AD) study on buntanetap, an experimental, oral translational inhibitor of neurotoxic aggregating proteins. The Phase II/III study is designed to enroll 320 patients with mild to moderate AD, randomized to receive either 7.5, 15, or 30 mg of buntanetap or placebo once daily. The co-primary endpoints are the change from baseline to the end of treatment of Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) and Alzheimer’s Disease Cooperative Study Clinician’s Global Impression of Change (ADCS-CGIC), assessing cognition and activities of daily living.
The interim analysis, based on 107 patients at six weeks, indicated that the trial should continue as planned with the same trial size to maintain statistical power for both co-primary endpoints. According to management, the fact that sample size re-estimation is unnecessary suggests that treatment effects in patients receiving buntanetap are positive compared to those receiving placebo after just six weeks of treatment.
Scholar Rock Expands into Cardiometabolic Disorders with Myostatin Inhibitor
Scholar Rock Holding Corporation (SRRK) announced its expansion into the cardiometabolic disorders space, leveraging its expertise in myostatin inhibition to advance SRK-439, a novel investigational myostatin inhibitor for treating cardiometabolic disorders, initially focusing on obesity. An Investigational New Drug (IND) application submission is targeted for 2025. Preclinical data support advancing SRK-439 for obesity treatment. Studies in diet-induced obese mice showed that SRK-439, in combination with a GLP-1 receptor agonist (GLP-1 RA), achieved a dose-dependent reversal of lean mass loss during GLP-1 RA-mediated weight loss and an increase in fat mass loss mediated by GLP-1 RA treatment.
Scholar Rock also plans to initiate a phase II proof-of-concept study with apitegromab in combination with a GLP-1 RA in 2024, pending IND acceptance. Data from the clinical trial are expected in mid-2025 and will be used to further advance clinical development of SRK-439.
Evelo Biosciences' Psoriasis Study Fails to Meet Primary Endpoint
Evelo Biosciences Inc. (EVLO) experienced a stock decline after announcing that its mid-stage study on EDP2939, an experimental candidate for treating moderate psoriasis, did not achieve its primary endpoint. The primary endpoint was the difference in the proportion of patients who achieved a 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score (a PASI-50 response) between EDP2939 and placebo after 16 weeks of daily treatment. Consequently, Evelo will cease the development of EDP2939 and is exploring strategic alternatives and partnering opportunities for its other candidate, EDP1815, and its small intestinal axis platform.
Amylyx Pharmaceuticals Receives Negative Opinion for AMX0035 in Europe
Amylyx Pharmaceuticals, Inc. (AMLX) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency confirmed its initial negative opinion on the Marketing Authorisation Application (MAA) seeking approval of AMX0035 for the treatment of amyotrophic lateral sclerosis (ALS) in the European Union (EU). Amylyx plans to focus on the completion of the phase III PHOENIX study, which was initiated prior to its MAA submission. Top-line results are expected in mid-2024. Amylyx plans to seek approval in the EU if the results of the PHOENIX study are positive.
