Marinus Pharmaceuticals Presents Clinical Data From Pivotal Phase 3 RAISE Trial in Refractory Status Epilepticus at the Neurocritical Care Society 2024 Annual Meeting

Business Wire 17-Oct-2024 7:00 AM

Marinus Pharmaceuticals, Inc. (NASDAQ:MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today presented new data from the pivotal Phase 3 RAISE trial evaluating intravenous (IV) ganaxolone for the treatment of refractory status epilepticus (RSE) at the Neurocritical Care Society (NCS) Annual Meeting. Topline data demonstrating that the trial met one of two co-primary endpoints were reported in June 2024.

In the RAISE trial (NCT04391569), patients with RSE that failed at least two antiseizure medications were randomized to IV ganaxolone or placebo in addition to standard of care treatment. The co-primary endpoints were the proportion of patients with status epilepticus (SE) cessation within 30 minutes and the proportion of patients not progressing to IV anesthesia within 36 hours of study drug initiation.

The RAISE trial prespecified secondary endpoints presented at NCS included:

• The median time to SE cessation: 4.2 minutes in patients treated with IV ganaxolone compared to 307.2 minutes for placebo (nominal p<0.0001).
• The proportion of patients with no escalation of treatment within 24 hours: 45% for IV ganaxolone compared to 19% for placebo (nominal p=0.0059).

Also presented were the previously reported RAISE topline results:

• A statistically significant proportion of patients achieved SE cessation within 30 minutes of initiating IV ganaxolone compared to placebo: 80% vs. 13%, respectively (p<0.0001).
• The trial failed to achieve statistical significance in the proportion of patients not progressing to IV anesthesia for 36 hours following initiation of IV ganaxolone compared to placebo: 63% vs. 51%, respectively (p=0.162).
• The median reduction in EEG seizure burden through 36 hours was 93% in patients treated with IV ganaxolone, compared to 36% for placebo (nominal p=0.003).
• The incidence of serious adverse events was similar between the treatment and placebo arms (n=19 for IV ganaxolone, n=18 for placebo), with hypotension being more commonly seen in the IV ganaxolone arm.

"The RAISE data presented today support that IV ganaxolone has the potential to play an important role in the treatment of RSE, demonstrating rapid cessation of SE as well as evidence of seizure control from EEG monitoring," said Brandon Foreman, M.D., M.S., FACNS, FNCS, Associate Professor of Neurology & Rehabilitation Medicine and Neurosurgery at the University of Cincinnati and Associate Director for Neurocritical Care Research, who presented the RAISE data in an oral session today.

Dr. Foreman continued, "With 80% of patients achieving SE cessation within 30 minutes of IV ganaxolone administration and a median time to SE cessation of 4.2 minutes, there is clear indication of rapid antiseizure activity in highly refractory patients. Although the RAISE trial did not achieve statistical significance on the second coprimary endpoint, other secondary measures of durability, such as reductions in EEG seizure burden and proportion of patients with no treatment escalation within 24 hours, showed clinically meaningful benefits."

"The findings we shared today underscore the potential of IV ganaxolone in the management of RSE, while also highlighting the challenges inherent in advancing research in this highly variable, complex disorder," said Joseph Hulihan, M.D., Chief Medical Officer of Marinus. "We have completed the first placebo-controlled trial in RSE, which has yielded important insights into the benefit ganaxolone could provide to these critically ill patients. We look forward to reviewing our data package with the FDA and discussing next steps for IV ganaxolone."

Ganaxolone development in the RAISE trial has been being supported in part by the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under contract number 75A50120C00159.

About Status Epilepticus

Status epilepticus (SE) is a life-threatening condition resulting from either the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures. SE is the one of the most common neurological emergencies in the U.S., affecting up to 150,000 patients each year, and is associated with substantial morbidity, mortality, and healthcare costs. Patients who do not respond to 1st- and 2nd-line treatments (benzodiazepines and intravenous antiseizure medications) are considered to have refractory SE (RSE).

About Intravenous (IV) Ganaxolone

Ganaxolone is a neuroactive steroid that works by modulating both synaptic and extrasynaptic GABA_A receptors via a unique binding site to potentiate two types of inhibitory signaling. IV ganaxolone has pharmacokinetic and pharmacodynamic properties well-suited for the treatment of status epilepticus. IV ganaxolone received orphan drug designation from the U.S. Food and Drug Administration for the potential treatment of status epilepticus.

About Marinus Pharmaceuticals

Marinus is a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for seizure disorders. The Company's product, ZTALMY^® (ganaxolone) oral suspension CV, is an FDA-approved prescription medication introduced in the U.S. in 2022. For more information, please visit www.marinuspharma.com and follow us on Facebook, LinkedIn and X.

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding Marinus, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may", "will", "expect", "anticipate", "estimate", "intend", "believe", and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements contained in this press release include, among others, the potential for IV ganaxolone to play an important role in the treatment of RSE and the potential next steps in the development of IV ganaxolone; as well as other statements regarding our commercial and clinical strategy, development plans and timelines and other future events.

Forward-looking statements in this press release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, unexpected actions by the FDA or other regulatory agencies with respect to our product candidates or products; competitive conditions and unexpected adverse events or patient outcomes from being treated with ZTALMY, uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; the company's cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the timing of regulatory filings for our product candidates; clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice of the FDA or EMA may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the size and growth potential of the markets for the company's product candidates, and the company's ability to service those markets; delays, interruptions or failures in the manufacture and supply of our product candidates; the company's ability to obtain additional funding to support its clinical development and commercial programs; and the company's ability to protect its intellectual property. This list is not exhaustive and these and other risks are described in our periodic reports, including our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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