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J10 Analysis of integrated safety data from pridopidine clinical trials demonstrates a favorable safety and tolerability profile at the clinically relevant dose of 45 mg bid
  1. Michal Geva1,
  2. Borje Darpo2,
  3. Georg Ferber3,
  4. Y Paul Goldberg1,
  5. Ralf Reilmann4,
  6. Michael R Hayden1,5
  1. 1Prilenia Therapeutics, Israel
  2. 2Clario, Rochester, NY, USA
  3. 3Statistik Georg Ferber GmbH, Riehen, Switzerland
  4. 4George Huntington Institute, Muenster, Germany
  5. 5CMMT, University of British Columbia, Vancouver, Canada


Pridopidine is a highly selective Sigma-1 receptor (S1R) agonist, being evaluated in the PROOF-HD Ph3 trial. Pooled safety data from 22 trials assessing pridopidine at doses 10-112.5 mg bid was analyzed, encompassing safety data from 1300 patients (~1300 patient-years of exposure, including long-term data >5 years); 1100/1300 (85%) HD patients, and 981/1300 (75%) treated with 45 mg bid, the dose assessed in PROOF-HD. Due to different placebo and pridopidine exposures, AE rate analyses, corrected for patient-years of exposure, were performed. The rate of common AEs was similar for placebo vs. 45 mg bid (rate=2.35 vs.1.82 events/patient years). Serious adverse events (SAEs) were reported in placebo and 45 mg bid groups (rate=0.07 and 0.18, respectively). Most SAEs were common for HD; 1 case of subdural hematoma was considered drug-related. Concentration-QTc analysis was performed using PK sampling and ECG monitoring data from 402 PRIDE-HD Ph2 trial participants, for 52 weeks. Pridopidine shows a concentration dependent effect on QTcF interval (slope=0.012 ms/ng/mL; 90% CI: 0.0109-0.0127). The, predicted QTc effect at 45 mg bid is 6.6 ms, with a two-sided 90% CI below 8 ms, that is of no regulatory concern (FDA considers QTc <10 ms low risk for Torsade de Pointes, TdP). Across the integrated safety database, the rate of AEs for QT prolongation was higher in placebo vs 45 mg bid (rate=0.013 vs. 0.005). No cases of TdP, and no increased risk for pro-arrhythmic events reported at the clinical dose. As of June 16th, 2022, PROOF-HD has low dropout (23/499, 4.6%) and discontinuation (19/499, 3.8%) rates. In February 2022, an independent safety monitoring committee reported no safety signals of concern, and recommended PROOF-HD continue as planned.

  • Pridopidine
  • safety
  • clinical trial
  • sigma-1 receptor

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