Tremor was the focus of the Phase 2 study of SAGE-324 (BIIB124), which did not show a statistically significant dose-response relationship on the primary endpoint in participants with essential tremor. There were no statistically significant differences between any dose of SAGE-324 and placebo in the change from baseline for the primary endpoint.
On July 24, 2024, Sage Therapeutics, Inc. (NASDAQ: Sage) and Biogen Inc. (NASDAQ: BIIB) announced the topline results from the Phase 2 KINETIC 2 dose-range study of SAGE-324 (BIIB124), an oral investigational drug for the potential treatment of essential tremor (ET). The study aimed to evaluate the efficacy, safety, and tolerability of SAGE-324, but the results showed that it did not achieve statistically significant improvements compared to placebo.
Tremor Study: Evaluation of SAGE-324 Shows No Significant Changes in Primary Endpoint
The primary endpoint of the study was the change from baseline to Day 91 based on the Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 (upper limb) total score. Additionally, the study assessed the TETRAS Activities of Daily Living (ADL) Composite Score. The KINETIC 2 Study enrolled 147 participants, including 129 on monotherapy and 18 on adjunct therapy with a stable dose of propranolol. Participants were randomized to receive either placebo or one of three doses of SAGE-324 (15 mg, 30 mg, or 60 mg with uptitration) for a three-month treatment period.
The results revealed that there was no statistically significant dose-response relationship for SAGE-324 in reducing upper limb tremor, as measured by the primary endpoint. Similarly, no statistically significant differences were found between any dose of SAGE-324 and placebo in the change from baseline to Day 91 on the TETRAS PS Item 4 Total Score or the TETRAS ADL Composite Score.
Given these outcomes, Sage and Biogen have decided to discontinue the ongoing open-label safety study of SAGE-324 in ET and do not plan to pursue further clinical development of SAGE-324 for this indication. The companies are now evaluating the next steps, if any, for other potential indications of the drug.
Dr. Laura Gault, Chief Medical Officer of Sage Therapeutics, expressed disappointment over the study results, stating, “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. We are grateful to the essential tremor community and study investigators for their contributions to this research.” She reaffirmed Sage’s commitment to developing new treatments for brain health conditions.
Tremor Study: Dr. Katherine Dawson Acknowledges Participant Contributions and Future Research Potential
Dr. Katherine Dawson, Head of Therapeutics Development Unit at Biogen, also commented, “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.”
The KINETIC 2 Study was meticulously designed to assess the dose-response relationship of different doses of SAGE-324 on upper limb tremor. The study also evaluated the safety and tolerability of the drug. The primary analysis focused on the dose-response relationship across various doses of SAGE-324, while additional analyses evaluated changes from baseline to Day 91 on both the TETRAS PS Item 4 Total Score and the TETRAS ADL Composite Score for each dose compared to placebo.
Overall, the study observed a dose-relationship in the incidence of central nervous system (CNS) depressant treatment-emergent adverse events (TEAEs) and in the frequency of TEAEs leading to study drug discontinuation. The most common TEAEs reported in any treatment group included somnolence, dizziness, fatigue, feeling abnormal, headache, and balance disorder, with the majority being mild or moderate in intensity.
The results from the KINETIC 2 Study highlight the challenges faced in developing effective pharmacological treatments for essential tremor, a condition that has seen limited innovation over the past five decades. While SAGE-324 did not meet the primary endpoint, the study contributes valuable data to the understanding of essential tremor and may guide future research and therapeutic strategies.
Sage Therapeutics and Biogen remain committed to their respective missions of advancing treatments for brain health conditions and neurological disorders. They continue to explore and develop new therapies that address the unmet needs of patients worldwide.
Resource: Business Wire, July 24, 2024
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