Sage Therapeutics and Biogen Officially Announce Ending of SAGE-324 Program in Essential Tremor
The KINETIC 2 study did not show statistically significant improvement in essential tremor symptoms compared to placebo, leading to the termination of its development for this condition.
Laura Gault, MD, PhD
Months after negative topline data was announced from the phase 2 KINETIC 2 study (NCT05173012) of SAGE-324 in essential tremor (ET), Biogen has officially terminated its rights under the collaboration and license agreement with Sage regarding the therapy’s program. The two companies will continue to partner on zuranolone (Zurzuvae), the first and only FDA-approved oral treatment for women with postpartum depression.1
According to the terms of the collaboration and license agreement, the partnership will officially end on February 17, 2025, at which point Sage will regain full ownership of the SAGE-324 asset. Moving forward, Sage intends to explore other possible indications, if any, for SAGE-324.
SAGE-324 is an investigational oral neuroactive steroid GABAA receptor positive allosteric modulator. In KINETIC 2, 147 patients with ET were randomly assigned to either placebo or SAGE-324 in doses of 15 mg, 30 mg, and 60 mg for a 3-month period. After 91 days of treatment, patients on SAGE-324 did not demonstrate statistically significant results in comparison with those on placebo for the primary end point of change in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 (upper limb) total score.
At the time of the announced data, in July, the two companies noted they would close the open-label study on terminate the development of SAGE-324 for ET. It was only a matter of time before the termination became official.
"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," Laura Gault, MD, PhD, chief medical officer at Sage, said in a statement regarding the KINETIC 2 trial.2 "We are disappointed that the results of the KINETIC 2 Study do not support further development of SAGE-324 in ET. We are grateful to the essential tremor community and study investigators for their contributions to this research. As always, Sage remains steadfast in our work to develop new treatments for people suffering from brain health conditions."
In KINETIC 2, investigators also saw a dose-dependent relationship between the incidence of central nervous system depressant treatment-emergent adverse events (TEAEs) and frequency of TEAEs leading to study discontinuation. In both placebo and active treatment groups, somnolence, dizziness, fatigue, feeling abnormal, headache, and balance disorder were the most commonly reported TEAEs, all of which were mild or moderate in severity.
SAGE-324 started to show promise in the original phase 2 KINETIC trial (NCT04305275), as treated patients in that study showed significant decreases in upper limb tremor relative to placebo after 29 days of treatment. All told, the study revealed a statistically significant reduction from baseline on TETRAS-PS Item 4 score in SAGE-treated patients vs placebo (–2.3 [SE, 0.401] vs –1.24 [SE, 0.349]; P = .0491), as well as significant least square mean reduction in a subgroup of patients on active treatment with severe baseline TETRAS-PS Item 4 score (at least 12; –2.75 [SE, 0.426] vs. –1.05 [SE, 0.412]; P = .0066).3
