Sage and Biogen Halt Phase II Study After Novel Drug Shows No Significant Improvement in Treating Essential Tremor

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Data from the Phase II KINETIC 2 study, which evaluated SAGE-324 (BIIB124) as a treatment for essential tremor (ET), show the drug did not achieve the trial’s primary objectives. According to Sage Therapeutics and Biogen, the study aimed to determine the dose-response relationship of SAGE-324 by assessing changes from baseline to day 91 in the TETRAS Performance Subscale Item 4 total score, measuring upper limb tremor severity. Results found that SAGE-324 offered no statistically significant improvement across different doses compared to placebo. As a result, both companies have decided to halt the ongoing open-label safety study and cease further clinical development of SAGE-324 for ET.¹

“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,” said Laura Gault, MD, PhD, chief medical officer, Sage Therapeutics, in a press release. “As always, Sage remains steadfast in our work to develop new treatments for people suffering from brain health conditions.”

The KINETIC 2 study, which was designed to evaluate the dose-response relationship of different doses of SAGE-324 on upper limb tremor, included 147 participants who were randomly assigned to receive SAGE-324 at doses of 15 mg, 30 mg, and 60 mg or a placebo over a three-month period. The study also evaluated the safety and tolerability of SAGE-324. Of the 147 participants, 129 were treated with a monotherapy and 18 with adjunct therapy. The primary endpoint of the study was a significant response in patients treated with SAGE-324 compared to placebo.

Results found that at day 91, there were no statistically significant differences between any dose of SAGE-324 and placebo in the change from baseline on the TETRAS PS Item 4 Total Score or TETRAS ADL Composite Score. Further, there was a dose-relationship observed in the incidence of central nervous system depressant treatment-emergent adverse events (TEAEs) and in the frequency of TEAEs leading to study drug discontinuation. The most commonly reported TEAEs were somnolence, dizziness, fatigue, feeling abnormal, headache, and balance disorder, which were mostly mild or moderate in intensity.¹

According to an analysis published in the American Academy of Neurology, approximately 6.4 million adults in the United States are currently living with ET, based on an overall prevalence of 2.6%. This prevalence is associated with increasing age, ranging from 0.8% among 18–30 year-olds to 8.2% among patients aged 85 years and older.2 ET effects an estimated 5% of the global population and mostly runs in families.3 Children of a parent with ET have a 50% chance of inheriting a gene that causes it. Commonly misdiagnosed as Parkinson disease, it is eight times more common, according to the National Institute of Neurological Disorders and Stroke. Currently, it is estimated that 60% of patients with ET don’t receive any benefit by medications available at this time.⁴

“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,” said Katherine Dawson, MD, head, therapeutics development unit, Biogen, in the press release.

Reference

1. Sage Therapeutics and Biogen Announce Topline Results from Phase 2 KINETIC 2 Study of SAGE-324 (BIIB124) for the Treatment of Essential Tremor. Biogen. July 24, 2024. Accessed July 24, 2024. https://investors.biogen.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-topline-results-phase-2

2. How many adults in the US have essential tremor? Using data from epidemiological studies to derive age-specific estimates of prevalence (4458). Neurology. April 14, 2020. Accessed July 24, 2024. https://www.neurology.org/doi/10.1212/WNL.94.15_supplement.4458#:~:text=An%20estimated%206.4%20million%20(M,%25)%20among%2085%20and%20older.

3. Essential Tremor. University of Michigan Health. Accessed July 24, 2024. https://www.uofmhealth.org/conditions-treatments/brain-neurological-conditions/essential-tremor

4. Facts about Essential Tremor. Essential Tremor. Accessed July 24, 2024. https://www.essentialtremor.org/wp-content/uploads/2013/07/FactSheet012013.pdf