RADNOR, Pa.–(BUSINESS WIRE)–Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare seizure disorders, today announced it has satisfied the FDA’s protocol-specific questions for the registrational Phase 3 trial (the RAISE trial) in refractory status epilepticus (RSE), allowing the company to begin enrollment in this clinical trial.
In July, Marinus submitted a protocol amendment to the FDA for the RAISE trial for IV ganaxolone in RSE. Following a recent FDA discussion, Marinus currently anticipates the first patient will be enrolled in the RAISE trial in October. To date, Marinus has selected over 55 out of a projected 80 clinical sites to participate in the trial. The company continues to anticipate top-line data in 1H 2022.
Marinus is also announcing the appointment of Henri Vaitkevicius, M.D., to the position of Vice President, Clinical Development, reporting to Joe Hulihan, M.D., Chief Medical Officer. During his time as a clinician at Massachusetts General Hospital, Harvard University Medical School, Dr. Vaitkevicius is credited as being the first physician to successfully treat a patient in super refractory status epilepticus with a neurosteroid.
Dr. Vaitkevicius joins Igor Grachev, M.D., Ph.D. and Maciej Gasior, M.D., Ph.D. in expanding Marinus’ clinical development team of physicians. Drs. Grachev and Gasior also hold the title of Vice President, Clinical Development.
“In our recent Phase 2 trial in RSE, status epilepticus was controlled at a median time of five minutes after starting ganaxolone, with no patients progressing to IV anesthesia for control of seizures within 24 hours, the primary study endpoint. There is a pressing need for better treatments for RSE, and we are eager to begin our Phase 3 clinical trial in this indication,” said Joe Hulihan, M.D., Chief Medical Officer. “Having served on our Scientific Advisory Board and as the principal study investigator in our Phase 2 RSE study, Henri has a solid understanding of the strong science behind our research and clearly shares our vision for developing ganaxolone as a treatment for patients with severe seizure disorders.”
Ganaxolone (GNX) development for RSE is funded, in part, by the Biomedical Advanced Research and Development Authority (BARDA) part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services under contract number 75A50120C00159.
Henri Vaitkevicius, M.D., Vice President, Clinical Development
Dr. Vaitkevicius was previously an attending neurologist in the Neurocritical Care, Stroke and Hospitalist Divisions of Brigham and Women’s Hospital Department of Neurology, and an Assistant Professor at Harvard Medical School. Dr. Vaitkevicius received his graduate and medical school training at Wayne State University in Detroit, Michigan. He completed his neurology residency and neurocritical care fellowship at Brigham & Women’s and Massachusetts General Hospital in Boston, Massachusetts.
“I have seen firsthand how devastating status epilepticus can be for patients and their families,” commented Dr. Vaitkevicius. “Despite the availability of many antiepileptic medications, patients often continue to have disabling seizures and suffer from countless life threatening side effects of currently available therapies. With the positive results from the RSE Phase 2 data, and the potential for the Phase 3 trial, I made a personal decision to leave 12 years of a successful clinical practice behind me in order to have an opportunity to contribute to the further development of ganaxolone. I am honored to be part of the Marinus team.”
Dr. Vaitkevicius has appeared in over 40 peer-reviewed publications, and multiple other scientific and medical materials and chapters. He has served as the director of Brain Hub: Studio for Research and Innovation in Critical Care Neurology, where he focused on fostering collaborations among academic departments and pharmaceutical industries to bring novel treatments to the bedside.
In connection with his appointment, Marinus granted Dr. Vaitkevicius a non-statutory stock option outside of the company’s 2014 Equity Incentive Plan as an inducement material to Dr. Vaitkevicius entering into employment with Marinus in accordance with Nasdaq Stock Market Listing Rule 5635(c)(4). The stock option to purchase 25,000 shares of the Marinus’ common stock was approved by the compensation committee of the company’s board of directors and has an exercise price of $8.44 per share, which is equal to the closing price on a split adjusted basis of the company’s common stock on September 14, 2020, the date of the grant. The stock option will vest and become exercisable as to 25 percent of the underlying shares on the one-year anniversary of the Dr. Vaitkevicius’ start date, and will vest and become exercisable as to the remaining 75 percent of the underlying shares in 36 equal monthly installments at the end of each month following such anniversary, subject to the Dr. Vaitkevicius’ continued employment with Marinus on such vesting dates.
Igor Grachev, M.D., Ph.D., Vice President, Clinical Development
Igor Grachev, M.D., Ph.D., joined Marinus as vice president, clinical development. He brings nearly 20 years of pharmaceutical industry experience to Marinus, having led clinical development and medical affairs programs at both multinational pharmaceutical and biotech organizations. Prior to joining Marinus, he served as chief medical officer at Cellectar Biosciences, and previously had progressive leadership roles at TEVA Branded Specialty Pharmaceuticals, Novartis, GSK, GE Healthcare, BioClinica, Merck, Sanofi-Aventis, Schering Plough, and Guide Pharmaceutical Consulting. Over the course of his career, Dr. Grachev has been responsible for clinical development, clinical operation, regulatory affairs, medical affairs and drug safety, execution and management of clinical programs and trials Phases 1 through four worldwide in neurology/neurodegenerative disorders and psychiatry, neuro-oncology and other adjacent therapeutic areas, achieving regulatory approvals in multiple countries.
Dr. Grachev is a former assistant professor at SUNY Upstate Medical University and served as a fellow/instructor/assistant professor at Massachusetts General Hospital, Harvard University Medical School. Dr. Grachev is well-published in the field of neurology, neurodegeneration and psychiatry with over 150 peer-reviewed publications. He is also the editor-in-chief of the Journal of Neurology and Brain Disorders and serves as associate editor of several neurology and medical journals. Dr. Grachev earned his M.D. with highest honor in general medicine from Bogomolets National Medical University; his Ph.D. in neuroscience, and neurology and psychiatry residency trainings from the Institute of Gerontology at the Shupyk National Medical Academy of Postgraduate Education; and completed a fellowship training at Massachusetts General Hospital, Harvard University Medical School.
Maciej Gasior, M.D., Ph.D., Vice President, Clinical Development
Maciej Gasior, M.D., Ph.D., joined Marinus as vice president, clinical development in 2018. Dr. Gasior has nearly 15 years of pharmaceutical experience. Prior to joining Marinus, he served as a senior medical director at TEVA Pharmaceuticals, where he led several R&D projects in the company’s pain portfolio that led to a regulatory approval. Other prior positions were with Bristol-Myers Squibb (Exploratory Clinical and Translational Research in Neuroscience and Pain) and Cephalon Inc. (Discovery and Clinical Research in CNS and Pain). Within these positions, Dr. Gasior was responsible for the clinical development and execution of global clinical programs and trials from Phases 1 through 4. Dr. Gasior is a former staff scientist in the Epilepsy Research Section (NIH-NINDS), junior faculty fellow at the Alcohol and Drug Abuse Research Center (Harvard Medical School) and post-doctoral fellow at the Drug Development Group (NIH-NIDA).
Dr. Gasior’s main research interests and expertise are in epilepsy, pain, and drug development for neuropsychiatric disorders. He has published over 90 papers in peer-reviewed journals, serves as a member of editorial boards for the Journal of Translational Neuroscience and Journal of CNS & Neurological Disorders – Drug Targets. He is also an adjunct professor of the Department of Pharmacology and Physiology (Drexel University College of Medicine). Dr. Gasior earned his M.D. with honors and Ph.D. in neuropharmacology from the Medical University of Lublin, Poland, where he is a full professor.
About the RAISE Trial
The Phase 3 RAISE Trial is a randomized, double-blind, placebo-controlled trial in SE patients who have failed benzodiazepines and two or more second line intravenous anti-epileptic drugs (AEDs). Approximately 80 study sites in hospitals across the U.S. will participate. The trial is designed to enroll approximately 125 patients, randomized to receive ganaxolone or placebo adjunctive to standard of care and to provide greater than 90 percent power to detect a 30 percent efficacy difference between ganaxolone and placebo.
Patients on ganaxolone will receive an IV bolus, then a 36-hour infusion followed by a 12-hour taper for a total 48-hour treatment period. This regimen targets a plasma concentration of greater than or equal to 500ng/mL for 12 hours (the same target concentration, for a 50 percent longer duration at this level compared to the Phase 2 trial).
The co-primary endpoints for the RAISE trial are (1) proportion of patients with SE cessation within 30 minutes of treatment initiation without other medications for the treatment of SE, and (2) proportion of patients with no progression to IV anesthesia for 36 hours following treatment initiation.
About Marinus Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare seizure disorders. Ganaxolone is a positive allosteric modulator of GABAA receptors that acts on a well-characterized target in the brain known to have anti-seizure, anti-depressant and anti-anxiety effects. Ganaxolone is being developed in IV and oral dose forms intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus recently completed the first ever Phase 3 pivotal trial in children with CDKL5 deficiency disorder and is conducting a Phase 2 trial in tuberous sclerosis complex, as well as a Phase 2 biomarker-driven proof-of-concept trial in PCDH19-related epilepsy. The company is planning to initiate a Phase 3 trial in status epilepticus. For more information visit www.marinuspharma.com.
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, statements regarding our clinical development plans for ganaxolone; our expectations to open clinical trial sites for our Phase 3 trial in status epilepticus in October; our expectations to release data from our Phase 3 RAISE trial in status epilepticus in 1H 2022; our expectations regarding our agreement with BARDA; the potential safety and efficacy of ganaxolone; and the therapeutic potential of ganaxolone. 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, uncertainties and delays relating to the design, enrollment, completion, results of clinical trials, and interpretation of clinical trial results; unanticipated costs and expenses; early clinical trials may not be indicative of the results in later clinical trials; clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; our ability to obtain and maintain regulatory approval for our product candidate; our ability to obtain and maintain patent protection for our product candidates; delays, interruptions or failures in the manufacture and supply of our product candidate; our ability to raise additional capital; the effect of the COVID-19 pandemic on our business, the medical community and the global economy; and the availability or potential availability of alternative products or treatments for conditions targeted by us that could affect the availability or commercial potential of our product candidate. Marinus undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see filings Marinus has made with the Securities and Exchange Commission.