Outlook Therapeutics Faces Setback in AMD Trial; Other R&D Updates
核心洞察
Outlook Therapeutics' ONS-5010 failed to meet the noninferiority endpoint in a Phase III wet AMD (搜索) trial, impacting company shares but BLA resubmission is still planned for early 2025.
The EMA revoked conditional marketing approval for Advanz Pharma's Ocaliva for primary biliary cholangitis (搜索) (PBC (搜索)) after a legal challenge failed.
Arovella Therapeutics is advancing ALA-101, a CAR-19-iNKT cell therapy, towards clinical trials for blood cancers and solid tumors, showing enhanced efficacy in preclinical studies.
Shares of Outlook Therapeutics Inc. experienced a significant drop following the release of preliminary data from the Norse Eight phase III trial. The trial assessed ONS-5010, an ophthalmic formulation of Avastin (bevacizumab, Roche AG (搜索)), for the treatment of wet age-related macular degeneration (搜索) (AMD (搜索)). While the drug demonstrated biologic activity, vision improvement, and a favorable safety profile, it did not meet the prespecified noninferiority endpoint at the eighth week, as defined in the special protocol assessment with the U.S. FDA. Despite this setback, Outlook Therapeutics plans to resubmit the BLA for ONS-5010 in the first quarter of 2025, with potential launch plans for later that year. The FDA previously issued a complete response letter in the summer of 2023 due to chemistry, manufacturing, and controls concerns.
Ocaliva's Conditional Approval Revoked in Europe
The conditional marketing approval for Ocaliva (obeticholic acid), a therapy for primary biliary cholangitis (搜索) (PBC (搜索)), has been revoked in Europe. This decision follows a dispute between the EMA and Advanz Pharma Ltd. (搜索), the company marketing the drug in Europe. Although Advanz Pharma initially secured a temporary suspension of the EMA's revocation decision, the court ultimately decided against extending the suspension, leading to the immediate revocation of the marketing authorization.
Arovella Advances CAR-iNKT Cell Therapy to Clinic
Arovella Therapeutics Ltd. (搜索) is preparing to initiate clinical trials for its lead product, ALA-101, a chimeric antigen receptor (CAR) therapy targeting CD19 (搜索) and utilizing invariant natural killer T (iNKT) cells. The company's approach combines iNKT cell technology with CARs to target both blood cancers and solid tumors. Preclinical studies have indicated that this combination therapy is more effective than conventional CAR T-cell therapy. Following a pre-IND meeting with the U.S. FDA, Arovella has a clear path forward for phase I trials of ALA-101, which is being developed as an allogeneic cell therapy.
Novel Signaling Pathway Identified
Researchers at the University of Copenhagen have discovered a signaling pathway that simultaneously increases energy expenditure and decreases food intake. Studies in humans and primates showed that agonists of the tachykinin NK2 receptor (搜索) (NK2R) led to both decreased food intake and increased energy expenditure. Behavioral tests suggested that these agonists do not cause nausea, a common side effect of GLP-1 agonists. The findings are published in Nature.
Immune System's Role in Neurodegenerative Diseases
At the recent HIF 2024 conference, Jun R. Huh, professor of immunology at Harvard Medical School, highlighted the role of the immune system in maintaining tissue homeostasis and its potential in treating neurological disorders such as autism spectrum disorder (搜索) (ASD (搜索)). Huh suggested that modulating the immune system, through activation or suppression of inflammation, could help correct historically difficult-to-treat disorders.
Scholar Rock's Apitegromab Set for BLA
Scholar Rock Holding Corp. (搜索) is preparing for a BLA submission for apitegromab after positive phase III results in patients with spinal muscular atrophy (搜索). Additionally, Visterra Inc. (搜索) reported positive top-line data from the Visionary phase III study of sibeprenlimab for immunoglobulin A nephropathy (搜索).