Sage and its partner Biogen said their experimental oral medicine failed a Phase 2 test in essential tremor and they will stop development in the nervous system disorder, which leads to involuntary shaking.
The results for SAGE-324/BIIB124 could determine whether they develop the drug in other indications. At the time of a 2020 pact, the companies said epilepsy and Parkinson’s disease could be additional areas for the drug. The bulk of that $3.1 billion tie-up, though, was focused on zuranolone, the drug approved last year for postpartum depression but rejected by the FDA for the larger major depressive disorder market. That rejection led Sage to lay off 40% of its workforce.
The companies said there was also a dose-relationship seen in the occurrence of “CNS depressant treatment emergent adverse events (TEAEs) and in the frequency of TEAEs leading to study drug discontinuation.” Side effects included somnolence, dizziness, fatigue and balance disorder, among others.
Sage’s shares $SAGE tanked nearly 25% before Wednesday’s opening bell. Biogen’s shares $BIIB were down a little more than 1%.
Laura Gault“There has been little innovation in the pharmacological treatment of essential tremor over the past 50 years, and people living with this debilitating condition have a pressing need for new treatment options. We are disappointed that the results of the KINETIC 2 Study do not support further development of SAGE-324 in ET,” Sage chief medical officer Laura Gault said in a press release.
Sage and Biogen are “evaluating the next steps, if any, for other potential indications” for SAGE-324, the companies said Wednesday morning. The companies have not launched clinical trials for those other indications.
The results come after another Sage drug, dalzanemdor, failed a Phase 2 in Parkinson’s earlier this spring.
In the KINETIC 2 study, 147 people received either placebo, 15 mg, 30 mg or 60 mg of the study drug for a three-month treatment period. Trial investigators did not observe a statistically significant dose-response relationship in change from baseline on the main goal, which honed in on upper limb tremor.
The drug is a neuroactive steroid GABAa receptor positive allosteric modulator. The companies said dysregulation of GABA, a key stabilizer of neuronal activity in the brain, has been “implicated in the pathophysiology of ET.”
In a prior Phase 2, the drug had just barely cleared the primary endpoint. The biotechs said SAGE-324 had narrowly achieved statistical significance on the reduction in upper limb tremor back in April 2021, coming in at a p-value of 0.049.