Patients were evaluated at day 29 for change in TETRAS item 4 score change from baseline.
Data from the phase 2 KINTETIC trial (NCT04305275) of SAGE-324 (also known as BIIB124), an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, evaluated in patients with essential tremor (ET), was presented at The International Parkinson and Movement Disorders (MDS) Society Virtual Congress 2021, September 17-22, finding that patients who received SAGE-324 showed significant decreases in upper limb tremor at day 29, when compared to patients who received placebo.
A total of 69 patients were randomized into the treatment group (n = 34) to receive a 60-mg dose of SAGE-324, or placebo (n = 35). Patients were evaluated on change from baseline score of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale item 4 (upper limb tremor score).
Evaluating the primary end point, investigators saw a statistically significant least-squared (LS) mean reduction of –2.31 (standard error [SE], 0.401), in TETRAS item 4 from baseline to day 29 (1 day after final dose) in patients treated with SAGE-324, compared to those receiving placebo, who had a –1.24 reduction (SE, 0.349; P = .049). Overall, those treated with SAGE-324 had a 36% reduction in upper limb tremor amplitude, when compared to baseline, while those receiving placebo experienced a 21% reduction.
“We believe the tremor reduction seen in the KINETIC study is clinically meaningful,” Helen Colquhoun, MD, vice president, early development, Sage Therapeutics, told NeurologyLive. “This study was designed to start to answer the question of tremor reduction over time vs the promising reduction we’ve previously seen at a single time point. To optimize the likelihood of seeing a drug effect, we dosed at 60 mg, the high-end of the dose range established in phase 1 studies. We also wanted to understand the AE profile at the 60-mg dose.”
When performing a subgroup analysis on patients with a median TETRAS item 4 score of greater than or equal to 12, those treated with SAGE-324 (n = 25) had a significant decrease of –2.75 (SE, 0.426), corresponding to a 41% reduction, compared to those receiving placebo (n = 22, who had a reduction of –1.05 (SE, 0.412), corresponding to a 18% reduction (P = .007).
Patients with ET included in the study were between the age of 18 to 80 years and had a score of greater than or equal to 10 points in TETRAS item 4. Those in the treatment group also experienced titration over the course of the study, as 19 patients (55.9%) had dosage reduced from 60 mg to 45 mg, 11 patients (32.4%) were reduced from 45 mg to 30 mg, and 2 patients (5.9%) were reduced from 60 mg to 30 mg. By the conclusion of the trial period, 24% had completed treatment on the 60-mg dose, 15% on the 45-mg dose, 24% on the 30-mg dose, and 38% discontinued treatment before completion.
Of the treatment-emergent adverse events reported among the treatment group, the most common were somnolence (67.6%), dizziness (38.2%), balance disorder (14.7%), fatigue (14.7%), diplopia (11.8%), dysarthria (11.8%), and gait disturbance (11.8%). Within the treatment group, 3 serious adverse events (SAEs) were reported, 2 of which were mental status changes related to treatment and resolved after patients discontinued 60-mg dosage of SAGE-324. Within the placebo group, 1 SAE was reported.
“ET is a serious and progressive condition that often steadily deteriorates over time, leading to social isolation and loss of independence. However, this underserved patient population has witnessed almost no innovation for over 50 years, and more than 50% of patients with ET do not respond optimally to the current standard of care,” Colquhoun said. “When you listen to patients, you realize that the tremor can affect nearly every aspect of day-to-day living and can make the simplest tasks difficult, if not impossible. We’ve learned that tremor can lead patients to feel frustrated and embarrassed, while others are left significantly disabled and unable to fully care for themselves.”
SAGE-324 continues to be developed as a treatment option for patients with ET, with plans for a phase 2b study to be initiated in late 2021.
For more coverage of MDS 2021, click here.