Applied Therapeutics’ lack of progress on govorestat as well as the potential costs to come have led analysts to question whether the biotech will ever be able to get the drug to market.
The New York-based company explained yesterday that it had finally received the official minutes from a meeting with the FDA back in September to agree on a path forward for govorestat. The drug is designed to treat Charcot-Marie-Tooth sorbitol dehydrogenase deficiency (CMT-SORD), a rare subtype of CMT that causes progressive, debilitating muscle weakness and sensory loss.
Applied Tx had previously said it was waiting for the minutes before it finalized the regulatory submission plan for the drug. But, in its third-quarter earnings release yesterday, the company implied the meeting had been less definitive.
“The FDA provided constructive feedback on the body of govorestat data submitted by the company and requirements needed to support a potential future NDA submission,” the biotech explained. “Key open issues included conclusive evidence for the pathophysiology of CMT-SORD, use of sorbitol levels as a surrogate endpoint, selection of a primary endpoint for a potential phase 3 trial, and carcinogenicity testing.”
Applied Tx said its next step will be to request another Type C meeting with the FDA.
“At this time, the company has not determined the specific path forward regarding a potential submission strategy for regulatory approval, including whether a future NDA submission would be made under the accelerated approval pathway,” Applied Tx said in the release.
“The company remains committed to advancing the development of govorestat for patients with CMT-SORD,” the biotech added.
Responding to Applied Tx’s update, analysts at William Blair questioned whether the biotech still has the funds to take the drug to market.
“Given that Applied had cash and cash equivalents of $11.9 million as of Sept. 30, we see the company as bearing increased financial risk from its limited cash runway and additional funding would be necessary to conduct an additional phase 3 trial,” the analysts wrote in a Nov. 13 note.
“Therefore, while we believe there could be a path forward for govorestat, in our view Applied is not in the position to advance the asset to commercialization at this time,” they added.
A phase 3 study for govorestat in CMT-SORD was posted on the federal trials database back in September, but that study’s status has remained as “not yet recruiting” ever since, despite an estimated start date of October.
Fierce has asked Applied Tx whether it believes the company has the resources to commercialize the drug alone or whether it's seeking a partner.
Back in May, Applied Tx said the drug missed in a phase 2/3 trial for CMT-SORD after failing to improve scores in a 10-meter walk-run test at 12 months when compared to placebo.
The company zeroed in on the study’s secondary endpoints, which included a statistically significant improvement in a patient-reported outcome measure and lowering blood sorbitol levels.
Applied Tx is also developing govorestat for other rare diseases, such as classic galactosemia.
In December 2024, the FDA rejected a new drug application for the drug in children with the disorder, while also reprimanding the biotech for the deletion of electronic data by a third-party vendor and the mishandling of a dosing error that led to some patients initially receiving lower levels of govorestat than intended.
Weeks after the FDA rebuff, Applied Tx’s CEO Shoshana Shendelman, Ph.D., departed, with Chief Financial Officer Les Funtleyder stepping in as interim CEO.
Funtleyder said in yesterday’s release that Applied Tx has “simultaneously … scheduled to meet with the FDA in the fourth quarter to review govorestat for the treatment of classic galactosemia.”
“We were also encouraged by new data from a single patient with PMM2-CDG, a severe, rare, and debilitating disease, treated with govorestat,” Funtleyder added. “These results … further support the potential for continued clinical development in this indication of high unmet need.”