- An experimental treatment developed by Sage Therapeutics for tremors met its primary goal in a mid-stage clinical study, appearing to significantly reduce shaking in the upper limbs by more than a third after 29 days of daily treatment.
- However, Sage's pill, which is part of a wide-ranging alliance with Biogen, caused sleepiness in more than two-thirds of study participants who took it and dizziness in more than one-third. More than half of treated patients had to reduce their dosage to deal with the side effects, leading some Wall Street analysts to question whether the drug, called SAGE-324, could succeed commercially.
- Results from the trial, called KINETIC, were the first data disclosed since Biogen bought rights to the drug in a collaboration that could be worth more than $3 billion. Biogen is hoping SAGE-324 and another experimental treatment for depression called zuranolone can help diversify its portfolio of neurological medicines, which is headlined by Alzheimer's drug prospect aducanumab.
The type of shaking that Sage hopes to treat is called essential tremor. The condition typically affects people as they age, and most frequently first appears in the hands, potentially making it difficult to write or eat. Only one drug, called propranolol, is approved to treat essential tremor based on results from a small study. Physicians use some epileptic drugs and barbiturates off-label as well.
Sage has been researching essential tremor for some time, having tested both its marketed depression drug Zulresso and lead pipeline project zuranolone in the condition. Both drugs have the same mechanism of action, but neither had the right combination of attributes — efficacy, tolerability and ease of administration — to move forward in a chronic condition like essential tremor. Sage searched for a better fit and came up with SAGE-324.
The Phase 2 KINETIC trial enrolled 69 patients and randomized them to take a 60 milligram daily tablet or a placebo. After 29 days, trial researchers measured the change in upper limb movement, part of a larger clinical assessment that physicians give to patients with essential tremor.
The 36% reduction in upper limb tremor amplitude from the study's start was statistically significant. Patients taking a placebo, by comparison, saw a 21% reduction.
The benefit appeared greater in a subset of patients with more severe disease. Those who fit that description and received SAGE-324 experienced a 41% reduction in upper-limb shaking, versus 18% of those who got placebo.
Yet the drug's side effect profile could prove challenging as Sage prepares for late-stage trials. Researchers recorded sleepiness in 68% of patients taking SAGE-324, dizziness in 38% and balance problems in 15%. Dose reductions were necessary for 62% of patients taking the pill — they were able to cut down to a 45 or 30 milligram daily dose — and 38% stopped taking the pill.
The side effects prompted Stifel analyst Paul Matteis to question whether physicians will be comfortable using SAGE-324 at the current dosing regimen. "[Physicians] with whom we spoke desire a new drug that is easy to prescribe without significant concerns surrounding adverse outcomes. One could argue this is more important than efficacy," Matteis wrote in an April 12 note to clients.
On a conference call Monday, Sage executives suggested they will be looking at the side effect profile as they prepare for a Phase 3 program, and hinted at advancing a lower dose. Chief Medical Officer Steve Kanes said the 60 milligram dose caused sleepiness in all patients in a Phase 1 trial, but because the Phase 2 trial was designed to show the dose could significantly reduce tremors they wanted to continue at that level.
"It truly gives us direction of where to go next, as we think about next steps for development," Kanes said.
Sage shares fell as much as 4% in Monday morning trading.