Ganaxolone was safe and well-tolerated
Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS) (“Marinus” or
“Company”), a biopharmaceutical company dedicated to the
development of innovative therapeutics to treat epilepsy,
depression and other neuropsychiatric disorders, today announced
positive results from its Phase 2 clinical trials evaluating
ganaxolone intravenous (IV) (the Magnolia Study) and oral (the
Amaryllis Study) in women with postpartum depression (PPD). Based
on these results, the Company is advancing both studies into the
next phase of development to evaluate IV and oral dose regimens.
“We achieved our Magnolia study objective and
are pleased with the early onset, magnitude and durability of
efficacy seen with ganaxolone IV over a month after treatment and
discharge from inpatient care,” said Dr. Lorianne Masuoka, Chief
Medical Officer of Marinus. “Ganaxolone IV’s safety profile
including ability to deliver even the highest dose at the start of
infusion in these patients makes it an attractive drug candidate
for this underserved patient population. The results from this
Phase 2 safety and pharmacokinetic dose-optimization study are
instrumental to future studies that incorporate our IV and provide
insight to further optimize our oral dose regimen.”
Magnolia Study Part 1 (Ganaxolone IV
Alone) Top-Line Data
- There was a clear dose response relationship seen for three
groups of patients receiving ganaxolone IV at median doses of 60,
90 and 140 µg/kg/h.
- The 140 µg/kg/h dose group (n=10) demonstrated the most robust
results, with a clinically meaningful 5.6-point reduction in
Hamilton Rating Scale for Depression (HAM-D17) compared to placebo
at 48 hours that was durable through the last visit, day 34.
- These patients had a mean HAM-D17 reduction of 16.9 (4.2 >
placebo) and 15.7 (4.1 > placebo) points from baseline at 60
hours and day 34, respectively.
- 75% of patients were responders, as defined as having a ≥50%
reduction from baseline, at day 34 and 67% were responders at 60
hours.
- 50% of patients achieved remission from depression, as
determined by a HAM-D17 ≤7, at day 34 and 33% achieved remission at
60 hours.
- Ganaxolone was safe and well-tolerated in all dose groups.
Consistent with previous ganaxolone studies, the most common
reported adverse events were sedation and dizziness. There
were no serious adverse events reported, no discontinuations due to
a treatment related adverse event and, consistent with prior
studies, there were no reports of syncope or loss of
consciousness.
- The Clinical Global Impression of Improvement (CGI-I) as well
as the Edinburgh Postnatal Depression Survey (EPDS) and Spielberger
State-Trait Anxiety 6 (STAI-6) showed highly similar trends that
were consistent with HAM-D17.
- 58 patients with PPD were randomized on a 1:1 basis to receive
one of three ascending fixed IV 60-hour dose regimens of ganaxolone
or placebo. No initial up titration was required, and patients were
down titrated over the final 12 hours of the 60-hour
infusion. A bolus injection of ganaxolone prior to the
60-hour infusion was explored to test the safety and tolerability
of a very short, high dose infusion. None of the dose groups
were powered to generate statistical significance.
- Patients with a HAM-D17 score of ≥26 were considered for
enrollment in the study. HAM-D17 measurements were conducted by a
centralized rater and taken at various timepoints spanning from
baseline to day 34.
Bassem Maximos, MD, MPH, FACOG, and a Principal
Investigator in the Magnolia Study, commented, “The impressive
safety profile and antidepressant effect demonstrated in these
women marks an important advancement in the development of
treatment of PPD. With no cure or approved treatment for the one in
seven women suffering from PPD, there is a great need for potential
treatment options that are safe, fast-acting and convenient. I look
forward to working with Marinus as they continue to develop both
the IV and oral formulations of ganaxolone.”
Amaryllis Study Update – Oral
GanaxoloneEnrollment is ongoing in the Company’s Amaryllis
study, a Phase 2 clinical trial to evaluate the safety,
tolerability and efficacy of oral ganaxolone in women with PPD.
Patients with a HAM-D17 score of ≥20 but <26 are being
considered for enrollment in the study. Cohorts of patients
enrolled in the initial open label phase of the study receive
ascending dose regimens with oral ganaxolone. The efficacy endpoint
is change from baseline in the HAM-D17 score.
Patients in the most recent dose cohort who took
oral ganaxolone (n=18) for four weeks had a mean HAM-D17 reduction
of 13.2 points 28 days from a baseline of 24.7 and a reduction of
15.7 points at day 36. This cohort is on-going and not all patients
have reached day 28. As with IV, oral ganaxolone was generally safe
and well-tolerated with no serious adverse events reported and no
discontinuations due to treatment related adverse events.
“Reporting these data from both of our PPD
studies is an important milestone for Marinus,” commented
Christopher M. Cashman, Chief Executive Officer of Marinus. “Based
upon these encouraging results, we are now equipped to enroll
patients into the next phase of development where we can explore
more convenient IV and oral dosing regimens. Ganaxolone’s efficacy
and clean safety profile provides the opportunity to develop a fast
acting, durable and convenient treatment regimen to meet the needs
of moms suffering from postpartum depression.”
The company is advancing both the Magnolia and
Amaryllis studies with data expected in the first half of 2019. The
second part of the Magnolia Study will evaluate a short IV infusion
followed by oral ganaxolone administration and the Amaryllis study
will continue to optimize oral ganaxolone dosing.
Marinus is planning to submit the full data set
from the Magnolia study for publication or presentation at a future
medical conference.
Conference Call and Webcast
DetailsMarinus will host a conference call today at 8:30
a.m. ET. Stockholders and other interested parties may participate
in the call by dialing 844-277-9448 (domestic) or 336-525-7135
(international) and referencing conference ID number 2197815. The
live webcast can be accessed on the investor page of Marinus’
website at https://ir.marinuspharma.com/. A replay will be
available on Marinus’ website approximately two hours after
completion of the event and will be archived for up to 30 days.
About PPDPPD is a mood disorder
that affects about 15% of women within the first year following
childbirth. Common symptoms include feelings of extreme sadness,
hopelessness, suicidal ideation, anxiety and fatigue. PPD is
thought to be linked to disorders of the GABA system, possibly
mediated by rapid fluctuations in the levels of reproductive
hormones and allopregnanolone (allo) after childbirth. Allo has
been shown in clinical studies to be effective in treating patients
with PPD. PPD can affect a mother’s ability to care for her child
and may negatively affect a child’s cognitive development. There
are no approved treatments for PPD, but the most common treatments
are psychotherapy and antidepressants.
About GanaxoloneGanaxolone, a
positive allosteric modulator of GABAA, is being developed in three
different dose forms (intravenous, capsule and liquid) intended to
maximize therapeutic reach to adult and pediatric patient
populations in both acute and chronic care settings. Unlike
benzodiazepines, ganaxolone exhibits anti-seizure and anti-anxiety
activity via its effects on synaptic and extrasynaptic
GABAA receptors. Ganaxolone has been studied in more
than 1,600 subjects, both pediatric and adult, at therapeutically
relevant dose levels and treatment regimens for up to four years.
In these studies, ganaxolone was generally safe and well-tolerated.
The most commonly reported adverse events were somnolence,
dizziness and fatigue.
About Marinus
Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a
biopharmaceutical company dedicated to the development of
ganaxolone, which offers a new mechanism of action, demonstrated
efficacy and safety, and convenient dosing to improve the lives of
patients suffering from epilepsy and neuropsychiatric disorders.
Ganaxolone is a positive allosteric modulator of GABAA 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 three different dose forms (IV, capsule and
liquid) intended to maximize therapeutic reach to adult and
pediatric patient populations in both acute and chronic care
settings. Marinus has initiated the first ever pivotal study
in children with CDKL5 deficiency disorder, a rare form of
epilepsy, and is currently conducting studies in women with
postpartum depression and refractory status epilepticus.
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”, “is planning”, 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 interpretation of
preclinical studies, development plans for our product candidate,
including the development of dose forms, the clinical trial testing
schedule and milestones, the ability to complete enrollment in our
clinical trials, interpretation of scientific basis for ganaxolone
use, timing for availability and release of data, the safety,
potential efficacy and therapeutic potential of our product
candidate and our expectation regarding the sufficiency of our
working capital. Forward-looking statements in this 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, the uncertainties inherent in the conduct of future
clinical trials, that results of preclinical studies or earlier
clinical trials are not necessarily predictors of future results in
later preclinical studies or clinical trials, the timing of the
clinical trials, enrollment in clinical trials, availability of
data from ongoing clinical trials, expectations for regulatory
approvals, the attainment of clinical trial results that will be
supportive of regulatory approvals, and other matters, including
the development of formulations of ganaxolone, and the availability
or potential availability of alternative products or treatments for
conditions targeted by the Company that could affect the
availability or commercial potential of our drug candidates.
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.
CONTACT: Lisa M. CaperelliExecutive Director,
Investor & Strategic RelationsMarinus Pharmaceuticals,
Inc.484-801-4674lcaperelli@marinuspharma.com
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