Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS), a biopharmaceutical
company dedicated to the development of innovative therapeutics to
treat epilepsy and neuropsychiatric disorders, today announced
top-line results from a Phase 2 exploratory open-label clinical
trial evaluating ganaxolone, its CNS-selective GABAA modulator, in
females with PCDH19 pediatric epilepsy. In the trial, ganaxolone
reduced seizure frequency from baseline in the majority of patients
enrolled in the study and was generally safe and well tolerated.
PCDH19 pediatric epilepsy is a rare, serious epilepsy characterized
by early-onset cluster seizures, cognitive and sensory impairment,
and behavioral disturbances, with no approved treatments. In 2015,
the U.S. Food and Drug Administration granted Orphan Drug
Designation to ganaxolone for the treatment of PCDH19.
Top-Line Results:
- 64% (7 of 11) of patients showed a seizure reduction compared
to baseline.
- 57% (4 of the 7 patients) showed a reduction of greater than
50% compared to baseline.
- 73% (8 of 11) of patients showed an increase in seizure-free
days.
- 73% (8 of 11) of patients showed CGI-I (Clinical Global
Impression of Improvement) scores of very much improved, much
improved or minimally improved at their last visit when
administered by the parent/caregiver, which correlated with overall
seizure reduction and participation in the study extension.
- Consistent with earlier studies, ganaxolone was generally safe
and well tolerated. The most common drug-related adverse event was
somnolence.
Michael
G. Chez, M.D., a pediatric neurologist at Sutter Medical Center in
Sacramento, California, and an investigator in the Phase 2 trial,
commented, “The benefit that ganaxolone provided in reducing
seizures is clinically meaningful for these difficult-to-treat
patients with a severe, rare epilepsy. Children with PCDH19
epilepsy are faced with many comorbidities that impact the quality
of life for them and their families. In addition to seizure
reduction, the patients that I treated with ganaxolone displayed
improved behavior and cognitive skills during treatment. A drug
that can lessen seizure burden and behavioral comorbidities caused
by this disease would be welcomed by patients, their families and
the medical community.”
The open-label Phase 2 exploratory study
enrolled 11 female children between 4 and 15 years of age at seven
sites in the United States and one site in Italy. Enrolled
patients had a confirmed PCDH19 genetic mutation and uncontrolled
seizures despite antiepileptic pharmacotherapy. Ganaxolone was
studied as an adjunctive treatment, administered as either oral
liquid suspension or capsules, for 26 weeks after establishing up
to 12 weeks of baseline seizure frequency. The primary efficacy
measure was the percent change in seizure frequency per 28 days
relative to the baseline. Secondary measures included percent
increase in seizure free days from baseline and evaluation of the
safety and tolerability of ganaxolone as adjunctive
therapy.
The following table summarizes selected key
efficacy measures for each patient:
Patient |
% Reduction in Seizure Frequency from
Baseline |
% Increase in Seizure Free Days from
Baseline |
1 |
|
100.0 |
% |
|
22.5 |
% |
2 |
|
72.8 |
% |
|
852.8 |
% |
3 |
|
69.5 |
% |
|
31.6 |
% |
4 |
|
53.8 |
% |
|
4.9 |
% |
5 |
|
26.6 |
% |
|
27.4 |
% |
6 |
|
18.7 |
% |
|
7.5 |
% |
7 |
|
2.6 |
% |
|
32.2 |
% |
8 |
|
(3.5 |
%) |
|
9.2 |
% |
9 |
|
(140 |
%) |
|
(2.9 |
%) |
10 |
|
(256 |
%) |
|
(9.7 |
%) |
11 |
|
(1031 |
%)* |
|
(89.5 |
%) |
*Seizure calendar data not verified
with caregiver
A majority of patients experienced reduced
seizures during ganaxolone treatment and elected to enter the study
extension following completion of 26-weeks of ganaxolone
treatment. All patients that experienced reduced seizures
also experienced an increased number of seizure-free days.
Ganaxolone was generally safe and well tolerated with
somnolence (4/11), headache (3/11), seizure (3/11) and fatigue
(3/11) reported as the most common drug related adverse events.
Three adverse events were reported as serious (one patient with
rash and two patients with seizures). Of the five patients
who discontinued the study, two patients discontinued due to lack
of efficacy and three due to an adverse event. Further data will be
presented in future publications and medical meetings.
Albena Patroneva, M.D., Chief Medical Officer of
Marinus Pharmaceuticals, commented, “I am excited by the positive
signal seen in this first proof-of-concept clinical study in
females with the rare genetic mutation of PCDH19. This clinical
trial confirms that the PCDH19 mutation affects every child
differently with respect to severity and frequency of seizures and
comorbidities. The knowledge gained from this study will be
invaluable in informing our overarching pediatric plan for
ganaxolone. We are now enrolling patients with other pediatric
genetic epilepsies who we believe are underserved by current
approved therapeutic options and who may benefit from ganaxolone
treatment.”
Marinus has expanded enrollment in this clinical
trial to include patients with CDKL5, Lennox-Gastaut Syndrome and
other pediatric genetic epilepsies. Data from these additional
patient populations will be available in 2017 and, along with
interactions with regulatory agencies, will inform the Company’s
future pediatric orphan clinical development strategy.
About PCDH19 Pediatric Epilepsy
PCDH19 pediatric epilepsy is a serious and rare
epileptic syndrome that predominantly affects females. The
condition, which is caused by an inherited mutation of the
protocadherin 19 (PCDH19) gene, located on the X chromosome, is
characterized by early-onset and highly variable cluster seizures,
cognitive and sensory impairment, and behavioral disturbances. The
PCDH19 gene encodes a protein, protocadherin 19, which is part of a
family of molecules supporting the communication between cells in
the central nervous system. In case of mutation, protocadherin 19
may be malformed, reduced in its functions or not produced at all.
The abnormal expression of protocadherin 19 is associated with
highly variable seizures, cognitive impairment and behavioral or
social disorders with autistic traits. Currently, there are no
approved therapies for PCDH19 pediatric epilepsy. No previous
formal clinical trials have been conducted in this population.
About Ganaxolone
Ganaxolone is a CNS-selective GABAA modulator
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. Ganaxolone acts on a well-characterized synaptic and
extrasynaptic GABAA target known for anti-seizure and
anti-anxiety activity. Ganaxolone has been studied in more
than 1,300 subjects, both pediatric and adult, at therapeutically
relevant dose levels and treatment regimens for up to two years. In
these studies, ganaxolone was generally safe and well tolerated,
with the most commonly reported adverse events of 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 CNS-selective GABAA modulator that acts on a
well-characterized target in the brain known to have both
anti-seizure 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.
Ganaxolone IV is in a Phase 1 clinical trial to treat status
epilepticus. Ganaxolone IV is complemented by its oral dose forms,
providing the potential for IV-to-oral continuation therapy for
patients transitioning from acute care to outpatient settings.
Ganaxolone capsule and liquid is being studied in orphan pediatric
indications with comorbidities in seizures and behavior disorders –
PCDH19, CDKL5, Lennox-Gastaut Syndrome, and Fragile X Syndrome. 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 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, the timing of
the clinical trials, enrollment in clinical trials, availability of
data from ongoing clinical trials, expectations for regulatory
approvals, and other matters, including the development of
formulations of ganaxolone, 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:
Company:
Lisa M. Caperelli
Senior Director, Investor Relations & Corporate Communications
Marinus Pharmaceuticals, Inc.
484-801-4674
lcaperelli@marinuspharma.com
Media Contact:
Tiberend Strategic Advisors, Inc.
Amy S. Wheeler
646-362-5750
awheeler@tiberend.com
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