Praxis Precision Medicines isn’t letting a midphase fail stand in the way of its plans in essential tremor. While its selective T-type calcium channel blocker failed to beat placebo on the primary endpoint, Praxis zeroed in on secondary measures and post hoc analyses to make the case for further development.
Investors didn’t seem quite as confident, however, sending the biotech’s stock plunging 47% to $1.53 per share in premarket trading from a Thursday closing price of $2.92.
The candidate, ulixacaltamide, is designed to improve the symptoms of essential tremor by normalizing burst firing in a sensory-motor network that is implicated in the disorder. To test that idea, investigators randomized 132 people with essential tremor, the most common movement disorder, to receive placebo or one of two regimens of ulixacaltamide.
After 56 days of daily oral dosing, the recipients of ulixacaltamide performed no better than their peers on placebo on the modified Activities of Daily Living (mADL) score, causing the study to miss its primary endpoint with a p-value of 0.126. No difference in efficacy was seen between the two dose regimens.
“The results … illustrate the clear potential of ulixacaltamide as an effective and well tolerated treatment for people with essential tremor,” CEO Marcio Souza said in the release. “The study showed meaningful improvement in patient’s daily functioning, while also providing insights to guide the program’s advancement to phase 3, including a deeper understanding of endpoints and trial design.”
Souza’s enthusiasm is underpinned by analyses beyond the headline result. For the primary endpoint, Praxis modified the standard ADL assessment by removing social impact from the scale and adding three other items. However, ulixacaltamide failed (PDF) to improve the three new items, but did improve social impact. On the standard ADL, the p-value was 0.026.
The FDA recommended that Praxis exclude social impact from its endpoint “because the responses can be affected by factors unrelated to tremor.” Praxis presented post hoc analyses that show ulixacaltamide beat placebo when the items added to the modified ADL primary endpoint were removed.
Based on the data, Praxis plans to start a phase 3 trial of ulixacaltamide in essential tremor in the second half of the year. Praxis’ cash will last into the first quarter of 2024.
Souza said it is now clear “that ADLs are the preferred endpoint for a registrational study for essential tremor.” Praxis is also studying the candidate in a midphase Parkinson’s disease trial, data from which are expected in the fourth quarter.