Applied Therapeutics has claimed a victory in its phase 3 SORD fight, setting up plans to talk to the FDA about filing for approval, although a flip-flopping stock price points to questions over the results.
New York-based Applied posted interim data from the phase 3 sorbitol dehydrogenase (SORD) deficiency rare disease trial Thursday. The company —which buried an earlier phase 3 failure more than 500 words into its press release—reported “positive interim 12-month results” from an ongoing study, “in which the primary endpoints and several key secondary endpoints were achieved.” The ClinicalTrials.gov entry has a list of four primary endpoints, with the 10-meter walk-run test at the top.
According to the biotech, the “12-month interim analysis was comprised of a clinical efficacy primary endpoint based on correlation of sorbitol with composite clinical outcome measures, and a pharmacodynamic biomarker primary endpoint based on sorbitol reduction.”
On that measure, Applied reported a statistically significant p-value of 0.05 in the study of govorestat, an aldose reductase inhibitor.
But analysts sought details of how patients performed on other measures on a conference call to discuss the data, prompting the following response from Applied CEO Shoshana Shendelman, Ph.D.: “We did see trends on the individual components of the 10-meter walk-run. Obviously, the level of impact was different on each of the different tests. I think, not surprisingly, we saw the strongest effects on 10-meter walk-run, six-minute walk and dorsiflexion, a little bit lower effects on four stair climb and sit to stand."
Later in the call, Shendelman highlighted the data on a patient-reported outcome, the CMT Health Index, as a positive surprise. Patients are “feeling that their mobility has improved, and that they have a better quality of life overall, they're less tired, they feel less pain,” the CEO said.
The study is continuing, but Applied plans to talk to the FDA about seeking approval on the strength of the interim data. Investors seemingly struggled to interpret the results, with Applied’s share price falling 11% at one point in premarket trading before climbing to $3.20, 19% above its starting position.
Applied has already filed for FDA approval of govorestat in another indication, galactosemia, and expects to receive feedback from the agency on that submission by the end of the month.
SORD is driven by sorbitol accumulation causing disability including loss of sensory function, neuromuscular dysfunction and decreased mobility. The biotech identified SORD as its next opportunity in light of evidence that aldose reductase, the enzyme inhibited by govorestat, converts glucose to sorbitol.