Supernus Pharmaceuticals has linked its mTORC1 activator to rapid improvements in adults with major depressive disorder (MDD) in a small trial, pointing to one possible path forward for a candidate that is barreling toward phase 2b data in another indication.
The open-label phase 2a trial assessed the effect of giving 40 adults with MDD 2400 mg of SPN-820 orally every three days. Supernus saw improvements on the HAM-D6 depression scale two hours after dosing. The 6.1-point reduction was clinically meaningful, according to the biotech, and deepened to a 9.6 decline by Day 10 of the trial.
Supernus saw a similar pattern of improvement on MADRS, another depression scale. Scores on MADRS fell 16.6 points in four hours. The reduction reached 22.9 points by Day 10. Again, Supernus said the data cleared the threshold for a clinically meaningful change, which the biotech put at a 6-7 point dip.
The biotech is now analyzing the remission and responder data, Supernus Chief Medical Officer Jonathan Rubin, M.D., said on a conference call to discuss the results. Rubin gave a glimpse at what to expect, noting that average MADRS scores fell to around 10. Johnson & Johnson defined remission as a score of 12 or less in its Spravato trial, backing Rubin’s view that a “high majority of people” on SPN-820 reached remission.
Two patients dropped out of the SPN-820 trial, one over hypertension that was unrelated to the study drug and another over noncompliance. No patients had serious adverse events. The top three adverse events were headache, nausea and somnolence, which affected 15% to 20% of participants.
“Our overall impression at this point is that it's really not that significant,” Rubin said about the six people with somnolence, a state of strong desire for sleep.
“Now, the bigger test will be in the larger study, the phase 2b study, which is ongoing, looking at the adverse event profile in drug and placebo, and seeing is there any difference between drug and placebo,” the CMO added. “Right now, we're just looking in a blinded fashion. What we're seeing is that this drug has a fairly benign safety profile.”
Supernus is aiming to share data from the phase 2b trial, which is testing SPN-820 in treatment-resistant depression (TRD), in the first half of next year. The biotech is holding off on deciding on the next steps in MDD until it sees phase 2b data. Supernus CEO Jack Khattar said he needs the data to decide “which way we're going to go with this drug, MDD or TRD, which one at first or maybe together in parallel.”
The biotech secured an option to license or acquire SPN-820, also known as NV-5138, from Navitor Pharmaceuticals in 2020 in return for a $10 million fee and a $15 million investment. Total payments could top $400 million.
Supernus placed that bet in the belief the fast onset of action, oral delivery and safety and tolerability profile of SPN-820 may set the candidate apart from existing depression drugs.