Govorestat failed to meet its primary endpoint in a Phase II/III trial for a rare form of Charcot-Marie-Tooth disease, a few months after the FDA rebuffed the same drug in a similar indication.
A few months after suffering a rejection at the hands of the FDA, Applied Therapeutics’ govorestat failed a late-stage clinical trial, the company announced Monday morning. The company’s stock, already worth only about $.50 per share, dropped another 16% after the market opened.
The drug was being tested by the New York–based biopharma in a Phase II/III INSPIRE trial for sorbitol dehydrogenase deficiency, a type of Charcot-Marie-Tooth (CMT) disease. The 56 patients in the trial were given once-daily govorestat or a placebo. After 12 months, govorestat failed to produce a statistically significant difference in a 10-meter walk-run test, the trial’s primary endpoint.
Sorbitol dehydrogenase deficiency (SORD), according to Applied’s statement, has only recently been identified as a specific subtype of CMT. The rare genetic disorder results in a sugar alcohol called sorbitol accumulating in nerves, creating muscle weakness and sensory loss.
In December 2024, the FDA rejected govorestat for a different but similar indication, galactosemia, a rare disease where patients experience build-up of the sugar galactose. The FDA cited “deficiencies” in the application, while Applied pledged to meet with the regulator to address its concerns.
In its statement announcing the INSPIRE data and failure, Applied reiterated its commitment to an NDA submission for govorestat in SORD sometime in 2025, focusing on positives that the drug has produced. For example, govorestat hit statistical significance on its secondary endpoint, a self-reported outcome measure of mobility and quality of life. The drug also reduced sorbitol measures in a preclinical rat model, according to Applied.
“In the midst of a complicated clinical landscape, we are encouraged by the breadth of data supporting govorestat’s ability to significantly lower blood sorbitol levels and positively impact both functional and patient-reported outcomes including stability and mobility at up to two years of treatment,” Evan Bailey, Applied’s senior vice president of clinical development, said in the statement. “We look forward to further analyzing the results from the INSPIRE trial to inform and support future potential regulatory interactions with the FDA regarding govorestat for the treatment of CMT-SORD.” The company last year said it had planned to submit an NDA for the indication sometime in the first quarter of 2025.
According to a note from William Blair analysts ahead of the INSPIRE data readout, Applied had requested a meeting with the FDA’s Office of Scientific Investigations to discuss next steps for the drug in galactosemia but was not granted a meeting.
