Praxis Precision Medicines’ challenge to Sage Therapeutics has unraveled. With a phase 2/3 clinical trial in major depressive disorder (MDD) failing comprehensively, Praxis is stopping work on a clutch of other studies, laying off staff and pinning its hopes on two other candidates.
The failed candidate, PRAX-114, is a type of nervous system drug known as an extrasynaptic GABAA receptor preferring positive allosteric modulator. Sage has gone some way toward validating the mechanism of action with its own drug zuranolone. Yet, Praxis’ bid to improve on the competition by providing a fast, durable antidepressant effect across MDD symptoms, a wider therapeutic window and simple nightly dosing has come unstuck.
Praxis is yet to share data from the phase 2/3 Aria trial, but everything that is known is bad. The study failed its primary endpoint, which looked at change in a depression score at Day 15, and missed all of its secondary endpoints.
“We are surprised and disappointed in the Aria study results,” Praxis CEO Marcio Souza said in a June 6 statement. “PRAX-114 was well-tolerated … yet the effect did not deliver to meet the needs of patients. Praxis is committed to our mission to help people suffering from CNS disorders and will prioritize our programs in movement disorders and epilepsy moving forward.”
The prioritization of the movement disorder and epilepsy programs will see Praxis lay off staff—it had 139 employees as of mid-February, up from 62 at the end of 2020—and stop work on other PRAX-114 trials. The biotech is also closing screening in its phase 2 Acapella study in MDD, positioning it to deliver results in the third quarter, stopping enrollment in a post-traumatic stress disorder phase 2 trial and discontinuing an essential tremor trial.
Through the changes, Praxis expects to extend its cash runway into 2024, giving it the time to rebuild its pipeline around its drugs PRAX-944 and PRAX-562. Top-line results from a phase 2b clinical trial of T-type calcium channel blocker PRAX-944 in the daytime treatment of essential tremor are due in the second half of the year, the same period given for epilepsy prospect PRAX-562 to enter phase 2 trials.
Praxis needs positive data on the candidates to drum up renewed enthusiasm for its pipeline. Shares in the biotech fell more than 60% to around $3 in premarket trading following news of the phase 2/3 flop.