- Trial met primary endpoint, median 28-day major motor seizure
frequency reduction of 32.2 percent compared to 4.0 percent for
placebo (p=0.002)
- Ganaxolone was generally well tolerated and the discontinuation
rate in the active treatment arm was less than 5 percent
- New Drug Application (NDA) submission planned for mid-2021;
commercial launch targeted for 1H 2022
- Conference call scheduled for September 14 at 4:30pm EDT
Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical
company dedicated to the development of innovative therapeutics to
treat rare seizure disorders, today announced positive top-line
results from its registrational Phase 3 clinical trial (Marigold
Study) evaluating the use of oral ganaxolone in children and young
adults with CDKL5 deficiency disorder (CDD), a rare, genetic
epilepsy with refractory seizures.
In the trial, patients given ganaxolone showed a significant
32.2 percent median reduction in 28-day major motor seizure
frequency, compared to a 4.0 percent reduction for those receiving
the placebo, achieving the primary endpoint (p=0.002). The trial’s
primary efficacy endpoint was the percentage change in 28-day
frequency of major motor seizures during the double-blind phase
relative to the 6-week prospective baseline period. Ganaxolone was
generally well tolerated with a safety profile consistent with
previous clinical studies. The most frequent adverse event was
somnolence.
Based on these results, Marinus plans to submit an NDA for
ganaxolone in the treatment of CDD to the U.S. Food and Drug
Administration (FDA) in mid-2021 and a Marketing Authorization
Application (MAA) for ganaxolone for the treatment of CDD to the
European Medicines Agency (EMA) by the end of Q3 2021.
“The Marigold Study has two important firsts. It’s the first
double-blind placebo controlled study providing evidence of
efficacy specific to CDD and the first Phase 3 trial to examine
three times a day dosing of ganaxolone in pediatric patients,” said
Scott Braunstein, M.D., Chief Executive Officer of Marinus
Pharmaceuticals. “We believe we are one step closer to providing
the first treatment indicated for CDD, and plan to continue our
investments in the oral ganaxolone franchise.”
The trial showed numerical trends favoring ganaxolone across
several predefined secondary endpoints, however, ganaxolone did not
meet statistical significance. Ganaxolone did meet statistical
significance in exploratory secondary endpoints.
“Today’s success with ganaxolone in CDD will pave the way for us
to accelerate our clinical studies in tuberous sclerosis complex
and possibly other rare pediatric epilepsies as well,” said Joe
Hulihan, M.D., Chief Medical Officer of Marinus. “We will continue
to explore the potential for ganaxolone’s unique mechanism of
action to address other areas of unmet medical need.”
The global, double-blind, placebo-controlled, Phase 3 trial
enrolled 101 patients. Children and young adults ages 2 to 21 with
a confirmed, disease-related CDKL5 gene variant were eligible to
enroll. Following a 6-week baseline period, trial participants were
randomized to receive either oral ganaxolone (up to 1,800 mg/day)
or placebo for 17 weeks, in addition to their existing anti-seizure
treatment. Following the double-blind phase, patients were eligible
to continue receiving ganaxolone in an open-label extension.
Marinus is planning to present the top-line results at an
upcoming scientific meeting.
“CDD is a severe genetic epilepsy that can cause hundreds of
seizures for patients each day,” commented Scott Demarest, M.D.,
Principal Investigator (PI) at Children’s Hospital Colorado; PI of
the International CDKL5 Clinical Research Network (ICCRN);
Assistant Professor of Pediatrics-Neurology at the University of
Colorado. “Existing antiepileptic medications fail to produce an
adequate and durable response in the majority of patients. The
positive results from Marinus’ trial demonstrate that ganaxolone
can provide significant seizure reduction in patients with CDD, an
important advance for the CDD community.”
The company plans to launch an Expanded Access Program (EAP) in
the fourth quarter, which will allow patients who were not able to
participate in the clinical trial to begin receiving treatment with
ganaxolone under a treatment protocol.
“CDD impacts each patient differently and is an incredibly
challenging form of epilepsy to treat,” commented Heidi
Grabenstatter, Science Director, International Foundation for CDKL5
Research. “Despite these challenges, as a patient community, we
have come a long way in helping to drive innovation. We are
grateful to Marinus for enabling researchers from across the globe
to establish a clinical trial network, connecting with patients in
need of care, and collaborating in a model for clinical research
that will benefit the CDD community and the greater rare disease
field in the future.”
Marinus will continue its pre-commercial development plans,
while simultaneously exploring commercialization opportunities for
ganaxolone in CDD with third parties to maximize access for CDD
patients.
Marinus has received a Rare Pediatric Disease (RPD) Designation
from the FDA for ganaxolone for the treatment of CDD. The FDA
grants an RPD Designation for diseases that affect fewer than
200,000 people in the U.S. and in which the serious or
life-threatening manifestations occur primarily in individuals 18
years of age and younger. If an NDA for ganaxolone in CDD is
approved, Marinus may be eligible to receive a priority review
voucher from the FDA, which can be redeemed for priority review in
a subsequent marketing application by Marinus or monetized by being
transferred to a third party. The program is intended to encourage
development of new drugs and biologics for the prevention and
treatment of rare pediatric diseases.
Corporate Update
In July, Marinus submitted a protocol amendment to the FDA for
its planned Phase 3 trial for IV ganaxolone in refractory status
epilepticus (RSE), and recently received FDA feedback on the
protocol. Currently, the company is engaging with the FDA to
respond to their feedback prior to enrolling patients in the trial.
To date, Marinus has selected 55 out of a projected 80 clinical
sites to participate in the trial. The company continues to target
top-line data in 1H 2022.
Marinus will also continue its Phase 2, placebo-controlled trial
of ganaxolone in PCDH-19-related epilepsy (Violet Study), with data
expected in the first half of 2021. As a result of COVID-19 related
delays in outpatient visits, Marinus plans on reporting data from
the Phase 2 trial in tuberous sclerosis complex (TSC) in mid-2021.
The company is planning to begin a Phase 3 registrational trial in
mid-2021 should the Phase 2 trial support moving forward to Phase
3.
Marinus earlier today announced a five-year cost-sharing
contract with the Chemical Medical Countermeasures division of the
Biomedical Advanced Research and Development Authority (BARDA),
part of the U.S. Department of Health and Human Services. This
agreement includes $21 million in non-dilutive funding to support
the Phase 3 clinical trial Marinus is planning in RSE and
preclinical studies of ganaxolone in nerve agent exposure animal
models, with up to approximately $30 million in additional optional
funding contingent on favorable clinical and preclinical outcomes.
The BARDA contract enables Marinus to expand development of
ganaxolone for treatment of RSE caused by nerve agent toxicity and
supports manufacturing, supply chain, clinical, regulatory, and
toxicology activities. Marinus will be responsible for cost-sharing
in the amount of $33 million if all development options are
completed.
Conference Call and Webcast
Marinus Pharmaceuticals' management will host a conference call
with a live webcast today, September 14 at 4:30 pm Eastern time to
discuss details of the trial findings and provide an overall
business update. To listen to the conference call, interested
parties within the U.S. should call +1-833-979-2765. International
callers should call +1-343-761-2590. All callers should ask for the
Marinus conference call. The conference call will also be available
through a live webcast, which can be accessed via the company’s
website at www.marinuspharma.com/investors. Please note that the
company will be using slides for this call, which are available on
the company’s website.
A replay of the call will be available approximately one hour
after the end of the call through September 21, 2020. The replay
can be accessed via the Company’s website or by dialing
+1-800-585-8367 or +1-416-621-4642. The replay conference playback
code is 7984226.
About CDKL5 Deficiency Disorder
CDKL5 deficiency disorder (CDD) is a serious and rare genetic
disorder that is caused by a mutation of the cyclin-dependent
kinase-like 5 (CDKL5) gene, located on the X chromosome. CDD is
characterized by early-onset, difficult-to-control seizures and
severe neuro-developmental impairment. Most children affected by
CDD cannot walk, talk, or feed themselves. Currently, there are no
therapies approved specifically for CDD.
About Ganaxolone
Ganaxolone, a positive allosteric modulator of GABAA receptors,
is being developed in intravenous and oral formulations intended to
maximize therapeutic reach to adult and pediatric patient
populations in both acute and chronic care settings. Unlike
benzodiazepines, ganaxolone exhibits antiseizure, antidepressant
and anti-anxiety activity via its effects on synaptic and
extrasynaptic GABAA receptors. More than 1,600 study participants,
both adults and children, have received ganaxolone at
therapeutically relevant dose levels and treatment regimens for up
to four years.
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 has conducted 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.
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 clinical
development plans for ganaxolone; our expectations to file an NDA
for ganaxolone for the treatment of CDD with the FDA by mid-2021;
our expectations to file an MAA for ganaxolone for the treatment of
CDD with the EMA by end Q3 2021; our expectations to begin
commercial launch of ganaxolone for the treatment of CDD in the
first half of 2022; our expectations to continue our investments in
the oral ganaxolone franchise; our expectations to present the
top-line CDD results at an upcoming scientific meeting; our
expectations regarding possible commercialization opportunities for
ganaxolone in CDD with third parties; our expectations to open
clinical trial sites for our Phase 3 trial in status epilepticus;
our expectations to release data from our Phase 3 trial in status
epilepticus in 1H 2022; our expectations to release top line data
from our Phase 2 open-label trial for patients with TSC in
mid-2021; our expectations to begin a Phase 3 registrational trial
in mid-2021; our expectations to release top line data from our
Phase 2 Violet Study in the first half of 2021; our expectations
regarding our agreement with BARDA; the potential safety and
efficacy of ganaxolone; expectations regarding our ability to
receive and utilize a priority review voucher; the therapeutic
potential of ganaxolone; and our plans for an expanded access
program for 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200914005828/en/
Sasha Damouni Ellis Vice President, Investor Relations &
Corporate Communications Marinus Pharmaceuticals, Inc. 484-253-6792
sdamouni@marinuspharma.com
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