Sage Therapeutics and Biogen have announced that they will discontinue further clinical development of SAGE-324 (BIIB124) for essential tremor (ET) after the KINETIC 2 study did not yield the desired results.
In the mid-stage study, the oral drug candidate could not show a statistically significant dose-response relationship in treating the neurological disorder.
According to the dose-range study, SAGE-324 failed to meet the primary endpoint. The trial’s primary endpoint was a statistically significant change from baseline to Day 91 in the Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 total score for participants with essential tremor.
The KINETIC 2 study also showed no significant differences between any dose of SAGE-324 and placebo for changes in TETRAS PS Item 4 Total Score or the TETRAS Activities of Daily Living (ADL) Composite Score.
In response to these findings, Sage Therapeutics and Biogen will terminate the ongoing open-label safety study of SAGE-324 in essential tremor. The companies are now reviewing potential next steps for other indications, if any.
Sage Therapeutics chief medical officer Laura Gault said: “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.”
The KINETIC 2 Study aimed to assess the dose-response relationship of various doses of SAGE-324 on upper limb tremor and to evaluate the drug’s safety and tolerability.
The primary outcome measure was the TETRAS PS Item 4 Total Score at Day 91, with additional analyses comparing changes from baseline to Day 91 on this measure and the TETRAS ADL Composite Score between SAGE-324 doses and placebo.
The study involved 147 participants, including 129 on monotherapy and 18 receiving adjunct therapy with a stable dose of propranolol before and during the study. Participants were randomly assigned to receive placebo, 15mg, 30mg, or 60mg (with uptitration) over a three-month treatment period.
Biogen therapeutics development unit head Katherine Dawson said: “We wish to thank the study participants and investigators who made this important research possible. While we share in their disappointment, we believe that the findings add to the collective understanding of this debilitating condition and may help inform the field on potential future research and therapeutic approaches.”
SAGE-324 is an investigational oral neuroactive steroid (NAS) GABAA receptor positive allosteric modulator (PAM), designed to enhance the inhibitory activity of the GABAergic system, which is the major inhibitory neurotransmission system in the brain.
In November 2020, Sage Therapeutics and Biogen had signed an agreement to jointly develop and commercialise SAGE-324 in the US for essential tremor and other neurological disorders.
