Marinus Pharmaceuticals Presents Clinical Data From Pivotal Phase 3 RAISE Trial in Refractory Status Epilepticus at the Neurocritical Care Society 2024 Annual Meeting
- Marinus Pharmaceuticals' Phase 3 RAISE trial demonstrated the efficacy of intravenous ganaxolone in rapidly ceasing seizures in patients with refractory status epilepticus, achieving a cessation rate of 80% compared to 13% with placebo within 30 minutes.
- While the RAISE trial met the endpoint for rapid seizure cessation, it did not achieve statistical significance in avoiding escalation to IV anesthesia, despite showing meaningful reduction in EEG seizure burden and treatment escalation needs.
- The data from the RAISE trial provide promising new insights for treating refractory status epilepticus, with Marinus Pharmaceuticals planning to submit findings to the FDA for potential approval, supported by funding from various health authorities.
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A New Hope for Seizure Disorder Treatment
In a significant milestone for the medical community, Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS) has presented clinical data from its pivotal Phase 3 RAISE trial, evaluating the safety and efficacy of intravenous (IV) ganaxolone in treating refractory status epilepticus (RSE) at the Neurocritical Care Society (NCS) Annual Meeting.
What is Status Epilepticus? Status epilepticus is a life-threatening neurological emergency characterized by prolonged or repeated seizures without full recovery in between. It affects up to 150,000 patients annually in the U.S., making it one of the most common neurological emergencies in the country.
Marinus Pharmaceuticals' Quest Marinus Pharmaceuticals has been at the forefront of developing innovative therapies to treat seizure disorders. Their focus on intravenous ganaxolone represents a promising new approach to managing RSE, which is particularly challenging due to its refractory nature. RSE is defined as status epilepticus that continues beyond 30 minutes or requires treatment escalation beyond standard first-line interventions.
The RAISE Trial: A Pivotal Moment The RAISE trial (NCT04391569) is a randomized, placebo-controlled study designed to evaluate the safety and efficacy of IV ganaxolone in patients with RSE who have failed at least two antiseizure medications. The trial's co-primary endpoints included the proportion of patients experiencing cessation of status epilepticus (SE) within 30 minutes and the proportion of patients not requiring escalation to IV anesthesia within 36 hours of initiating the study medication.
Key Findings from the RAISE Trial
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Rapid SE Cessation: The trial demonstrated a statistically significant proportion of patients achieving SE cessation within 30 minutes of initiating IV ganaxolone compared to placebo. Specifically, 80% of patients treated with IV ganaxolone achieved SE cessation within 30 minutes, compared to just 13% in the placebo group (p<0.0001).
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Median Time to SE Cessation: The median time to SE cessation was significantly shorter in patients treated with IV ganaxolone, at 4.2 minutes, compared to 307.2 minutes for those receiving placebo (nominal p<0.0001).
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EEG Seizure Burden Reduction: The trial also showed a substantial reduction in EEG seizure burden through 36 hours. Patients treated with IV ganaxolone experienced a median reduction of 93%, whereas those on placebo saw a reduction of 36% (nominal p0.003).
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Treatment Escalation: Another significant finding was that a higher proportion of patients treated with IV ganaxolone did not require escalation of treatment within 24 hours. Specifically, 45% of patients in the ganaxolone group did not need treatment escalation, compared to 19% in the placebo group (nominal p0.0059).
Challenges and Future Directions
While the trial met one of its two co-primary endpoints, it did not achieve statistical significance for the second co-primary endpoint related to avoiding IV anesthesia escalation. Despite this, other secondary measures demonstrated clinically meaningful benefits. The data presented underscore the potential of IV ganaxolone in rapidly controlling seizures in highly refractory patients, albeit with some challenges inherent in managing this complex disorder.
Implications for Patient Care
The findings from the RAISE trial offer new hope for patients with RSE. Rapidly controlling seizures can significantly improve patient outcomes and reduce the risk of long-term neurological damage. The ability to quickly cease ongoing seizures with IV ganaxolone represents a major advancement in the treatment paradigm for RSE.
Next Steps
Marinus Pharmaceuticals is now preparing to submit its data package to the U.S. Food and Drug Administration (FDA) for review. This step is crucial in determining whether IV ganaxolone will become a new treatment option for refractory status epilepticus. The company's Chief Medical Officer, Joseph Hulihan, M.D., highlighted the importance of this milestone, noting that the insights gained from the RAISE trial have provided valuable insights into the potential benefits of ganaxolone for critically ill patients.
Support and Funding
The development of ganaxolone in the RAISE trial has been supported in part by the Department of Health and Human Services; Administration for Strategic Preparedness and Response; and the Biomedical Advanced Research and Development Authority (BARDA) under contract number 75A50120C00159.
Conclusion
Marinus Pharmaceuticals' presentation of clinical data from the pivotal Phase 3 RAISE trial marks a significant milestone in the fight against refractory status epilepticus. The rapid and effective cessation of seizures achieved with IV ganaxolone offers a promising new treatment option for patients with this life-threatening condition. As the medical community continues to explore innovative therapies, the RAISE trial data provide essential insights into the future of RSE management.
References:
- Marinus Pharmaceuticals. Status Epilepticus.
- https://marinuspharma.com/focus-areas/status-epilepticus-se/
- Business Wire. Marinus Pharmaceuticals Presents Clinical Data From Pivotal Phase 3 RAISE Trial in Refractory Status Epilepticus at the Neurocritical Care Society 2024 Annual Meeting.
- https://www.businesswire.com/news/home/20241017642755/en/Marinus-Pharmaceuticals-Presents-Clinical-Data-From-Pivotal-Phase-3-RAISE-Trial-in-Refractory-Status-Epilepticus-at-the-Neurocritical-Care-Society-2024-Annual-Meeting
- Yahoo Finance. Marinus Pharmaceuticals Presents Clinical Data From Pivotal Phase 3 RAISE Trial in Refractory Status Epilepticus at the Neurocritical Care Society 2024 Annual Meeting.
- https://finance.yahoo.com/news/marinus-pharmaceuticals-presents-clinical-data-110000074.html
This article aims to provide a comprehensive overview of the groundbreaking clinical data presented by Marinus Pharmaceuticals from its pivotal Phase 3 RAISE trial. The RAISE trial's findings have significant implications for the treatment of refractory status epilepticus, offering new hope for patients suffering from this life-threatening condition.
