Applied Therapeutics received a positive signal from the FDA regarding its New Drug Application (NDA) for govorestat, a treatment for classic galactosemia. The FDA has canceled the planned advisory committee meeting, indicating a potentially smoother path to approval. This decision has significantly boosted investor confidence, leading to a surge in Applied Therapeutics' stock price.
Regulatory Update and Market Reaction
The FDA's decision to forgo the advisory committee meeting suggests that the agency is comfortable with the data submitted for govorestat. The Prescription Drug User Fee Act (PDUFA) target decision date remains November 28, 2024. Following the announcement, Applied Therapeutics' stock price jumped 72%, reflecting the market's optimism. Analysts from William Blair and Baird have expressed favorable views on the development, anticipating potential labeling discussions with the FDA soon.
Analyst Perspectives
Lachlan Hanbury-Brown from William Blair noted that the FDA's decision is a positive sign, indicating comfort with the clinical data. Brian P. Skorney from Baird suggested that the cancellation reflects broader favorable developments within the agency's review process. Joseph P. Schwartz from Leerink Partners increased the probability of success (PoS) for govorestat's approval from 70% to 85%, citing substantial upside potential in both galactosemia and SORD deficiency indications. Leerink also raised its 12-month price target for Applied shares by 27%, from $11 to $14.
Govorestat's Potential
Govorestat (AT-007) is a central nervous system (CNS) penetrant aldose reductase inhibitor designed to treat rare neurological diseases, including galactosemia and SORD deficiency. It works by blocking the conversion of glucose to sorbitol. Leerink Partners forecasts worldwide peak sales for govorestat in classic galactosemia at approximately $870 million by 2035. Applied Therapeutics has partnered with Advanz Pharma for commercial rights in Europe, potentially receiving over €130 million in milestone payments and royalties.
Clinical Data and Regulatory Pathway
The FDA's acceptance of Applied's NDA was based on data from the Phase III ACTION-Galactosemia Kids trial, the Phase I/II ACTION-Galactosemia trial, and preclinical data. While the ACTION-Galactosemia Kids trial did not meet statistical significance on the primary endpoint (p < 0.05), it showed consistent clinical benefit across functional measures (p = 0.1030). A pre-specified sensitivity analysis including cognition showed improvement (p = 0.0698). Biomarker data indicated a 40% reduction in mean plasma galactitol, which was statistically significant versus placebo.
Implications for Rare Disease Treatment
Analysts suggest that the FDA's decision on govorestat could be influenced by its recent approval of Zevra Therapeutics' arimoclomol for Niemann-Pick disease type C (NPC). This indicates the agency's flexibility in reviewing rare disease treatments with high unmet needs but controversial efficacy data. Govorestat has also been granted the FDA’s Rare Pediatric Disease Designation, potentially qualifying Applied for a Priority Review Voucher (PRV) upon approval.
Other Company Updates
In other company news, Achilles Therapeutics announced cost-cutting measures, including ending development of its TIL-based cNeT therapy. Corbus Pharmaceuticals Holdings' shares declined following Phase IIb data for a Novo Nordisk weight loss candidate. Edgewise Therapeutics' shares increased after positive topline data from trials assessing its cardiac sarcomere modulator EDG-7500. NuCana's shares initially surged after positive data from a Phase II trial of NUC-7738 and Merck's Keytruda in metastatic melanoma but later declined.
