Encouraging Initial Clinical Data for Praxis’ PRAX-222 in SCN2A Gain-of-Function DEE
First in-human data for PRAX-222, an antisense oligonucleotide (ASO) in development for SCN2A gain-of-function was reported during a Praxis R&D day. This is the first clinical trial readout in SCN2A which represents an exciting milestone for our SCN2A community. To date, there have been 5 patients dosed with this therapy (4 patients in their clinical study EMBRAVE, and an additional newborn patient with a poor prognosis treated through expanded access). Praxis reported a seizure benefit in treated patients and didn’t disclose any treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) related to the study drug. Praxis plans to initiate a global pivotal study in 2024 after they compile and discuss their data with the FDA.
No Safety Signals is a Positive Signal
Initial clinical studies are designed to test and evaluate the safety and tolerability of the drug in development, and the initial safety profile of PRAX-222 was clean. PRAX-222 was well tolerated by patients, and there were no treatment-emergent adverse events or serious adverse events related to the study drug disclosed by Praxis. Furthermore, the patient treated under expanded access had the longest treatment exposure (7 doses, monthly treatment) and also experienced no serious adverse events.
Seizure Reductions Reported in Each Patient Treated
There was a 44% median seizure reduction following three doses of PRAX-222 (monthly intrathecal administration) in EMBRAVE with benefits also being observed in the percentage of seizure-free days experienced by the patients. Additionally, the patient treated under expanded access had their status epilepticus cease, experienced a reduction seizure frequency, and is now clinically stable. This data is still early (the number of treated patients is small and there is no control arm as a baseline-) but these are encouraging initial data for PRAX-222 and the SCN2A gain-of-function community.
Efficacy at 1 mg Dosing Would Be a Win
1 mg is a relatively low dose for an ASO (with many CNS programs dosing 10x to 100x more than this). Efficacy at a lower dose would be a positive because: 1. It would have a higher probability of a strong safety profile. There is a general belief that lower dosing means lower probability of safety issues with ASO and with the functional heterogeneity of SCN2A mutations it may also give more flexibility to safely select patients; 2. It means there is a considerable amount of room to increase the dose to optimize the efficacy profile in patients that may need that; and 3. Efficacy in early studies may speed up time to approval and distribution to our community (vs. spending meaningful time titrating dose to find an efficacy signal).
Next Steps for the Program
Recruiting is closed for this portion of the trial but Praxis expects to expand the study to a global pivotal trial in 2024 after a meeting with the FDA to discuss this data and next steps.
For more on these results see our interview with the Praxis management team here and for more information on eligibility for the study see study site EMBRAVE.
Frequently Asked Questions
Drugs typically have to clear multiple clinical trial hurdles in order to support approval. The typical trial phases are 1, 2, and 3 with lower number being earlier trials and larger numbers being more advanced trials.
Phase 1 trials are typically in healthy volunteers and are evaluating initial safety, and dosing in humans. These trials help ensure that the drug is safe enough to be evaluated in patients and also are used to identify an appropriate dosing range for subsequent trials.
Phase 2 trials are typically used to provide proof of concept (that the drug has an efficacy signal, is providing a benefit to patients) and also tests safety in the patient population. These trials often are used to help design and power registrational phase 3 trials.
Phase 3 trials are often the trials used to support the approval of the agent and may be the final clinical hurdle a drug needs to pass in order to be approved by the FDA.
This is a designation granted by the FDA when a drug is being developed to treat a pediatric condition that is serious and life-threatening and occurs in under 200k people in the US.
This is a program used by the US government to incentivize drug development for pediatric rare diseases. If a drug is approved that has been granted the rare pediatric disease designation, then the developing company receives a voucher that grants priority review of a future drug (which can accelerate the developmental time of a drug by ~4 months; for example: if drug#1 is approved and had been granted the rare pediatric disease designation then said company would receive a priority review voucher that they could use on drug#2 ).
This is a designation granted by the FDA when a drug is being developed to treat a rare disease (occurs in under 200k people in the US).
This is a program used by the US government to incentivize drug development for rare diseases. Drugs awarded this designation received a number of incentives by the FDA including: 1. Market exclusivity for 7 years post approval, 2. A waiver of application of user-fees, and 3. A 50% tax credit for clinical testing expenses