Praxis Precision Medicines, Inc. (PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today provided an update on its Phase 2a proof of concept study evaluating PRAX-628 in epilepsy patients with PPR. PPR studies measure electroencephalogram (EEG) signatures after intermittent photic stimulation and are used as an indicator of anti-seizure efficacy.
“The strength and consistency of response across both study arms, combined with a continued positive tolerability and safety profile, build on our earlier conviction that PRAX-628 has the potential to be the first precision sodium channel modulator for focal epilepsy patients. With such a clear response, we have advanced our planning of the focal epilepsy efficacy study for PRAX-628, expected to begin in the second half of 2024. We extend our thanks to the patients who participated in this PPR study,” said Marcio Souza, president and chief executive officer of Praxis.
| Summary of Response | |||
| Cohort | Partial Response Rate | Complete Response Rate | Total Response |
| 15mg | 20% (1) | 80% (4) | 100% (5) |
| 45mg | -- | 100% (3) | 100% (3) |
| Combined | 12% (1) | 88% (7) | 100% (8) |
About the Phase 2a PPR Study
- Patient EEG signatures were assessed at defined measurement points over a 24-hour period after receiving placebo or PRAX-628, and results were compared to baseline.
- Patients must have demonstrated PPR during screening and baseline to be evaluable.
- A total of six patients were baselined in the 15 mg cohort, of whom five were evaluable. One patient in the 15 mg cohort did not present adequate PPR at baseline to be evaluated.
- Four patients were baselined in the 45 mg cohort, of whom three were evaluable. One patient in the 45 mg cohort was not evaluable due to lack of eligibility.
- Three patients from the 15mg cohort participated in the 45mg cohort after a washout period of >100 days.
- Three patients were on background anti-seizure medications (ASMs).
- Response Assessment
- Complete: Reduction to zero in the number of generalized PPR events at any assessment period vs. baseline.
- Partial: Reduction, other than to zero, in the number of generalized PPR events at any assessment period vs. baseline.
- Safety and PK samples were collected during the entire observation period.
PRAX-628 for Focal Epilepsy:
- The Phase 2a study builds on positive results from animal studies and the Phase 1 dose escalation study in healthy volunteers.
- PRAX-628 demonstrated unprecedented pre-clinical efficacy in the maximal electroshock seizure (MES) model.
- PRAX-628 was generally well-tolerated at all tested doses in the Phase 1 study.
- Pharmacokinetic data from the Phase 1 study demonstrated dose-dependent exposure supporting once-daily dosing without titration to achieve potentially therapeutically effective drug concentration levels.
- Further analysis of patients in the Phase 1 study using quantitative EEG data showed a pharmacodynamic effect at all dose levels and was significantly different from placebo.
Praxis will host a call on Tuesday, March 26 at 8:00 am ET to discuss the study results, and will be joined by Dr. Daniel Friedman, Professor of Neurology at NYU Grossman School of Medicine. To register for the call, please click here.
The live webcast and replay will be available through the Events & Presentations page of the Investors and Media section of the company’s website at www.praxismedicines.com.
About PRAX-628PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset epilepsy. Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, PRAX-628 has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of PRAX-628 have demonstrated unprecedented potency in the MES model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50.