RAISE trial met its first co-primary endpoint
demonstrating rapid cessation of status epilepticus in a highly
refractory patient population
The trial failed to achieve statistical
significance on the second co-primary endpoint of the proportion of
patients not progressing to IV anesthesia
Marinus will continue to prioritize the ZTALMY®
franchise and expansion opportunities in highly refractory, chronic
epilepsies with Phase 3 TrustTSC topline data expected in the first
half of Q4 2024
As a result of recently implemented cost
reduction plans and financing activity, the Company projects cash
runway into Q2 2025
Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical
company dedicated to the development of innovative therapeutics to
treat seizure disorders, today announced topline results from the
Phase 3 double-blind, randomized, placebo-controlled RAISE trial
(NCT04391569) evaluating the safety and efficacy of intravenous
(IV) ganaxolone for the treatment of refractory status epilepticus
(RSE). RSE, in which prolonged continuous or rapidly recurring
seizures do not respond to first- and second-line therapy, is
associated with significant morbidity and mortality.
In the RAISE trial, 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 intent-to-treat
population consisted of 96 patients, including 49 in the IV
ganaxolone arm and 47 in the placebo arm.
Topline data demonstrated that:
- The trial met the first co-primary endpoint: A
statistically significant proportion of patients had status
epilepticus cessation within 30 minutes of initiating IV ganaxolone
compared to placebo: 80% vs. 13%, respectively (p<0.0001).
- The trial did not meet the second co-primary endpoint:
RAISE 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 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.
“Although the RAISE trial did not achieve statistical
significance on one of its co-primary endpoints, these findings
provide valuable insights that will guide our ongoing research and
development in our mission to bring innovative and effective
treatment options to those in need,” said Scott Braunstein, M.D.,
Chairman and Chief Executive Officer of Marinus. “We would like to
thank the patients, families, investigators and their clinical
trial sites for their contributions to this important
research.”
Joseph Hulihan, M.D., Chief Medical Officer of Marinus
commented, “We are proud to have conducted the first randomized
Phase 3 trial in patients with refractory status epilepticus, a
highly variable and complex seizure disorder. We noted that
patients were enrolled late in their course of status, with study
drug initiated, on average, 38 hours following onset. This appears
to be inconsistent with the urgency to initiate therapy emphasized
in treatment guidelines.”
Dr. Hulihan added, “Also disappointing to us was the imbalance
in baseline characteristics between the two treatment arms, with a
higher proportion of patients in the IV ganaxolone arm presenting
with stupor or coma, entering the trial on mechanical ventilation,
having a higher baseline status epilepticus severity score, and
higher incidences of underlying disorders associated with
significant morbidity and mortality, such as glioblastoma and
encephalitis. We believe this imbalance confounds the assessment of
potential differences in patient outcomes for IV ganaxolone
compared to placebo.”
Marinus continues to believe in the potential of IV ganaxolone
as a treatment for RSE, supported not only by the rapid onset of
its antiseizure effect but also the objective evidence of status
epilepticus control observed with an additional analyses of
continuous electroencephalogram (EEG) monitoring. Preliminary EEG
analyses indicate patients receiving IV ganaxolone demonstrated
durable reductions in seizure burden through 36 hours with an 88%
median reduction compared to 38% for placebo. This suggests that
the need for IV anesthesia was driven by factors other than status
severity and may not represent an accurate measure of seizure
control.
“Stopping status epilepticus as quickly as possible is critical,
as each passing minute heightens the risk of permanent neurologic
impairment,” said Aatif M. Husain, M.D., Epileptologist,
Neurologist, Professor in the Department of Neurology, and Chief of
the Division of Epilepsy, Sleep, and Clinical Neurophysiology at
Duke University Medical Center. “The findings in the RAISE trial
indicate that objective measures such as EEG should be considered
in future trials to assess control of status epilepticus rather
than endpoints dependent on a proxy measure such as use of IV
anesthesia.”
The Company will continue to analyze the full RAISE dataset and
plans to engage with the U.S. Food and Drug Administration to
discuss a potential path forward for IV ganaxolone in RSE. Marinus
expects to present the RAISE data at an upcoming medical
meeting.
Marinus intends to continue to offer IV ganaxolone for patients
with super refractory status epilepticus under emergency
investigational new drug applications.
The Company expects cash and cash equivalents are sufficient to
fund its operating expenses, including capital expenditure and
working capital requirements, into the second quarter of 2025. The
projection includes the impact of cost reduction plans announced
earlier this quarter and recent amendments to Marinus’ existing
credit agreement with Oaktree Fund Administration, LLC, and
Marinus’ Revenue Interest Financing Agreement with Sagard
Healthcare Royalty Partners, LP.
Ganaxolone development in the RAISE trial has been 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 GABAA 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 first introduced FDA-approved prescription medication
ZTALMY® (ganaxolone) oral suspension CV in the U.S. in 2022. For
more information about Marinus visit www.marinuspharma.com.
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, statements regarding our plans to continue to
prioritize the ZTALMY franchise and expansion opportunities in
highly refractory, chronic epilepsies; our expected data readouts;
our intention to continue analyzing the full RAISE dataset and to
engage with the FDA to discuss a potential path forward for IV
ganaxolone in RSE; our expectations to present the RAISE data at an
upcoming medical meeting; our intention to continue to offer IV
ganaxolone for patients with super refractory status epilepticus
under emergency investigational new drug applications; our
expectation that our cash and cash equivalents are sufficient to
fund our operating expenses, including capital expenditure and
working capital requirements, into the second quarter of 2025;
statements regarding our expected clinical development plans,
enrollment in our clinical trials, regulatory communications and
submissions for ganaxolone, and the timing thereof; the safety and
efficacy of ganaxolone, as well as its therapeutic potential in a
number of indications; and other statements regarding our future
operations, financial performance, financial position, prospects,
objectives 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 results or delays in the commercialization
of ZTALMY; unexpected market acceptance, payor coverage or future
prescriptions and revenue generated by ZTALMY; unexpected actions
by the FDA or other regulatory agencies with respect to our
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 varying
interpretation of clinical data; our ability to comply with the
FDA’s requirement for additional post-marketing studies in the
required time frames; the timing of regulatory filings for our
other product candidates; the potential that regulatory
authorities, including the FDA and EMA, may not grant or may delay
approval for our product candidates; 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 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; our ability to obtain and
maintain regulatory approval for our product candidate; our ability
to develop new formulations of ganaxolone or prodrugs; our ability
to obtain, maintain, protect and defend intellectual property for
our product candidates; the potential negative impact of third
party patents on our or our collaborators’ ability to commercialize
ganaxolone; delays, interruptions or failures in the manufacture
and supply of our product candidate; the size and growth potential
of the markets for our product candidates, and our ability to
service those markets; our ability to continue as a going concern;
our cash and cash equivalents may not be sufficient to support our
operating plan for as long as anticipated; our expectations,
projections and estimates regarding expenses, future revenue,
capital requirements, and the availability of and the need for
additional financing; our ability to obtain additional funding to
support our clinical development and commercial programs; the
potential for our ex-U.S. partners to breach their obligations
under their respective agreements with us or terminate such
agreements in accordance with their respective terms; the risk that
drug product quality requirements may not support continued
clinical investigation of our product candidates and result in
delays or termination of such clinical studies and product
approvals; 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. This list is not exhaustive and these and other
risks are described in our periodic reports, including the annual
report 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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version on businesswire.com: https://www.businesswire.com/news/home/20240617609407/en/
Company Contacts
Investors Sonya Weigle SVP, IR, HR
& Corporate Affairs Marinus Pharmaceuticals, Inc.
sweigle@marinuspharma.com
Media Molly Cameron Director,
Corporate Communications & Investor Relations Marinus
Pharmaceuticals, Inc. mcameron@marinuspharma.com
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