Jazz’s Suvecaltamide Fails to Meet Primary End Point in Phase 2b Trial of Essential Tremor

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Suvecaltamide did not meet the primary endpoint in the phase 2b trial but showed numeric improvements and was well-tolerated.

Rob Iannone, MD, MSCE, executive vice president and global head of Research and Development at Jazz

Rob Iannone, MD, MSCE

In a company update, Jazz Pharmaceuticals announced that its investigational agent suvecaltamide, otherwise known as JZP385, did not achieve its primary end point of statistical significance vs placebo in a phase 2b trial (NCT05122650) of adults with essential tremor. Designed as a highly selective and state-dependent modulator of T-type calcium channels, suvecaltamide will continue to be assessed in its ongoing phase 2 trial (NCT05642442) of Parkinson disease (PD) tremor, with results expected in the first quarter of 2025.

The phase 2b study, a 12-week, multicenter, double-blind, randomized, placebo-controlled trial comprised of 420 participants from 4 countries, used change in the modified Essential Tremor Rating Assessment Scale (TETRAS) composite outcome score as the primary end point. Overall, the therapy failed to significantly distinguish itself from placebo on TETRAS; however, numeric improvements were observed with the active agent. Although not statistically significant, suvecaltamide-treated patients also showed numeric improvements over placebo on Clinical Global Impression-Severity (CGI-S) scale, a secondary end point.

Jazz noted that the improvements in the placebo group over the 12-week period exceeded the company’s expectations and were higher than what was previously observed for placebo in the prior T-CALM trial of suvecaltamide. Throughout the trial, the therapy was considered safe and well-tolerated, with no new safety signals observed. Among treated patients, the most common treatment-emergent adverse events (TEAEs) were dizziness, headache, paresthesia, diarrhea, and insomnia, most of which were mild to moderate in severity. Of note, there was a serious AE related to study treatment, although the specifics of it were not disclosed.

"We are disappointed that the trial did not meet its primary endpoint. We recognize the significant unmet need for people living with ET, and we are grateful to the patients, their families and the investigators that participated in the trial,” Rob Iannone, MD, MSCE, executive vice president and global head of Research and Development at Jazz, said in a statement.1 "We are evaluating the data to better understand the trial results and await the results of the suvecaltamide trial in Parkinson's disease tremor to determine next steps for the program. The Phase 2 Parkinson's disease tremor trial is ongoing with results expected first quarter 2025."

READ MORE: Parkinson Therapy ND0612 Receives Complete Response Letter

The trial assessed the efficacy and safety of once-daily oral dose of 10, 20, or 30 mg of suvecaltamide in patients aged 18 to 80 with essential tremor. Patients were to have moderate to severe disability associated with tremor as determined by scores greater than 22 on the TETRAS-Activities of Daily Living subscale, as well as a CGI-S rating of at least moderate for participants’ ability to function. The phase 2b study excluded those with evidence of severe cognitive impairment, suicidal risk, a history of substance use disorder, or prior MRI-guided focused ultrasound thalamotomy, among other exclusions.

Earlier this year, at the 2024 American Academy of Neurology Annual Meeting, investigators presented the design of the ongoing phase 2 proof-of-concept trial of suvecaltamide in patients with moderate to severe residual PD tremor. This double-blind, placebo-controlled, flexible-dosing, parallel-group, multicenter study will enroll 160 participants with PD, aged 40-85 years old, with inadequately controlled tremor despite optimized treatment with PD medications. In a 5-week titration period, participants will receive suvecaltamide 5 mg/day for 1-2 weeks, increasing to 10 mg/day for 1 week, then increasing by 10 mg/day once weekly up to 30 mg/day to optimize efficacy and tolerability.

A 12-week maintenance period follows the titration period. Over the complete 17-week period, patients will be judged on changes on TETRAS composite score, the primary end point. Additional end points include assessments of PD symptoms, clinician and participant global impressions, embarrassment/quality of life due to tremor, and safety and tolerability.

REFERENCES
1. Jazz Pharmaceuticals provides update on phase 2b trial of investigational suvecaltamide (JZP385) in essential tremor. News release. June 20, 2024. Accessed June 20, 2024. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-provides-update-on-phase-2b-trial-of-investigational-suvecaltamide-jzp385-in-essential-tremor-302177347.html
2. Skarpaas T, Hauser R, Adler C, et al. Design of a phase 2 study of suvecaltamide in moderate-to-severe Parkinson’s disease tremor. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. ABSTRACT P9-3.009.
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