Adamas Presents Positive Phase 1a Data of ADS-4101 (lacosamide) for the Treatment of Partial Onset Seizures in Epilepsy
May 22 2017 - 8:30AM
-- Phase 1 results show ADS-4101 is better
tolerated in healthy volunteers than equivalent doses of VIMPAT®
(lacosamide) immediate-release tablets --
Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced a
presentation of positive data from the Phase 1a clinical trial of
ADS-4101 (lacosamide) modified-release capsules, in a podium
presentation at the 14th Antiepileptic Drug and Device Trials
Conference. ADS-4101 was derived from the company’s drug
development platform and is in development for the treatment of
partial onset seizures in patients with epilepsy. This Phase 1a
study showed that single 400 mg doses of ADS-4101 in healthy
volunteers have improved tolerability compared to the equivalent
dose of VIMPAT® (lacosamide) immediate-release (IR) tablets. The
data informed the selection of a formulation that is suitable for
further clinical evaluation.
“We have successfully confirmed our hypothesis
that the rapid initial rise in blood levels contributes to the
adverse event profile of lacosamide, allowing us to advance
ADS-4101 forward in clinical development,” said Gregory T. Went,
Ph. D., Chairman and Chief Executive Officer of Adamas
Pharmaceuticals, Inc. “The goal of this program is to achieve
higher levels of lacosamide throughout the day when we believe
patients with epilepsy are most prone to seizures with similar or
better tolerability than VIMPAT (lacosamide). ADS-4101 could
potentially be the fourth product to emerge from Adamas’
proprietary drug development platform, and potentially a second
product for Adamas to commercialize for the benefit of patients
with neurologic disorders.”
ADS-4101 Phase 1a Trial Results
The ADS-4101 Phase 1a study was an open-label, single dose,
cross-over study in 24 healthy volunteers that was designed to
assess the pharmacokinetics (PK) and tolerability of four 400 mg
dose formulations of ADS-4101 compared with VIMPAT tablets and to
guide the selection of an ADS-4101 formulation for further clinical
development.
Data from the study showed all four formulations
of ADS-4101 to be safe and well tolerated when compared to the
VIMPAT-treated group. Table 1 displays the most common adverse
events occurring within 24 hours for all four formations of
ADS-4101 compared to VIMPAT-treated patients following a single
400mg dose. Most adverse events for VIMPAT occurred within the
first four hours following treatment.
Table 1. Adverse Events for ADS-4101 formulations compared
to VIMPAT (lacosamide) IR tablets |
|
ADS-4101 Formulations |
VIMPAT |
|
1 |
|
2 |
|
3 |
|
4 |
|
|
|
400 mg (N=12) |
400 mg (N=12) |
400 mg (N=12) |
400 mg (N=10) |
400 mg (N=24) |
Subjects with At Least One Adverse Event within 24 Hours |
16.7 |
% |
33.3 |
% |
16.7 |
% |
10.0 |
% |
62.5 |
% |
Most Common AEs with onset within 24 Hours by
Preferred Term |
Hypoesthesia, oral |
0.0 |
% |
8.3 |
% |
0.0 |
% |
0.0 |
% |
45.8 |
% |
Dizziness |
8.3 |
% |
8.3 |
% |
8.3 |
% |
10.0 |
% |
33.3 |
% |
The Phase 1a study also showed that the ADS-4101
formulations have a slower rise and prolonged time to maximum
plasma concentrations (Tmax) compared to VIMPAT tablets. The time
to max plasma concentrations for the ADS-4101 formulations ranged
from 9.5 – 17.0 hours compared to 0.5 – 1.0 hour for VIMPAT
tablets. The data from the Phase 1a study guided the company’s
decision to select a formulation for further clinical evaluation,
which is well tolerated, rises slowly and has a 15-hour time to
maximum concentration.
“With this positive data in hand, coupled with
our understanding that epileptic seizures primarily occur during
the day, we have advanced our program to evaluate three ascending
doses of ADS-4101 in healthy volunteers,” said Rajiv Patni, M.D.,
Chief Medical Officer of Adamas Pharmaceuticals, Inc. “The ongoing
Phase 1b steady state study is designed to establish the dose and
titration schedule of ADS-4101 given once daily at bedtime. We look
forward to topline data from this study in the third quarter, with
the goal of advancing to clinical studies in epilepsy patients
following a meeting with FDA.”
ADS-4101 Phase 1b Clinical Trial
DesignBased on positive findings from the Phase 1a study
of ADS-4101, Adamas has initiated a multi-dose Phase 1b study
designed to evaluate the tolerability and PK profile of three
ascending doses of ADS-4101 administered once daily at bedtime
compared to ascending doses of twice daily VIMPAT tablets in 24
healthy volunteers. The objectives of the study are to determine
the steady-state PK parameters of the three dose levels of ADS-4101
and three dose levels of VIMPAT tablets as well as to compare
overall safety and tolerability of ADS-4101 versus VIMPAT tablets.
Over a three-week period, ADS-4101 is dosed once daily at nighttime
starting at 200 mg for Week 1, increasing to 400 mg for Week 2 and
600 mg in Week 3, compared to twice daily doses of VIMPAT tablets
at 100 mg twice daily in Week 1, 150 mg twice daily in Week 2 and
200 mg twice daily in Week 3. Topline data from the ADS-4101 Phase
1b study are expected in the third quarter of 2017.
About ADS-4101iThere is an
important need for new, clinically differentiated treatment options
for epilepsy, a chronic neurologic disorder characterized by
recurrent unprovoked seizures, affecting an estimated 2.2 million
Americans. Nearly two-thirds of epilepsy patients suffer from
partial onset seizures, which affect one side of the brain. Despite
advances, nearly one-third of epilepsy patients continue to suffer
from seizures.
ADS-4101 is an investigational drug in
development for the treatment of partial onset seizures in patients
with epilepsy. Derived from Adamas’ development platform, ADS-4101
is a high strength lacosamide therapy administered once daily at
bedtime. Lacosamide is an anti-epilepsy active ingredient
previously approved by the U.S. Food and Drug Administration and
currently marketed as VIMPAT® (lacosamide). ADS-4101 is designed to
deliver high concentrations of medicine during the day when
seizures primarily occur and achieve higher drug levels throughout
the day when Adamas believes patients with epilepsy are most prone
to seizures, with similar or better tolerability than VIMPAT.
About Adamas Pharmaceuticals,
Inc.Adamas develops new medicines to improve the daily
lives of those affected by chronic neurologic disorders, including
Parkinson’s disease, multiple sclerosis, epilepsy, and Alzheimer’s
disease. Adamas has pioneered a platform to develop medicines for
chronic neurologic disorders based on an understanding of the
time-dependent biologic processes responsible for disease activity
and drug response to potentially achieve symptomatic relief without
tolerability issues. The company’s most advanced product candidate,
ADS-5102, is a high-dose amantadine, taken once daily at bedtime,
in development for levodopa-induced dyskinesia in people with
Parkinson’s disease and walking impairment in people with multiple
sclerosis. A New Drug Application supporting ADS-5102 for the
treatment of levodopa-induced dyskinesia in people with Parkinson’s
disease is under review by the FDA with a PDUFA date of August 24,
2017. Adamas is exploring other indications of ADS-5102 for further
development. Adamas is also investigating ADS-4101 for the
treatment of partial onset seizures in patients with epilepsy.
Additionally, Adamas’ licensed assets, are currently marketed by
Allergan under the brand names NAMENDA XR® and NAMZARIC®, and
Adamas is eligible to receive royalties on sales of these medicines
beginning in June 2018 and May 2020, respectively. For more
information, please visit www.adamaspharma.com.
NAMENDA XR® and NAMZARIC® are trademarks of Merz
Pharma GmbH & Co. KGaA.VIMPAT® is a trademark of UCB.
Forward-looking Statements
Statements contained in this press release regarding matters that
are not historical facts are "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995, including but not limited to, statements contained in this
press release regarding the potential additional data on ADS-4101,
and potential efficacy and safety of ADS-4101 for the treatment of
partial onset seizure in patients with epilepsy. Words such as
"expect," "anticipate," and similar expressions (as well as other
words or expressions referencing future events, conditions, or
circumstances) are intended to identify forward-looking statements.
Because such statements are subject to risks and uncertainties,
actual results may differ materially from those expressed or
implied by such forward-looking statements. For a description of
risks and uncertainties that could cause actual results to differ
from those expressed in forward-looking statements, including risks
relating to the timing and potential success its products,
including ADS-4101; the regulatory and competitive environment for
products covered by patents with limited term and scope of
exclusivity protection; and Adamas' business in general, see
Adamas' Annual Report on Form 10-K filed with the Securities and
Exchange Commission on May 9, 2017. Investors are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date of this release. Adamas undertakes no
obligation to update any forward-looking statement in this press
release.
i Epilepsy Foundation of America 2016;
Datamonitor Epidemiology Report 2013 American Association of
Neurological Surgeons 2016
Contact:
Martin Forrest
Vice President, Corporate Communications & Investor Relations
Adamas Pharmaceuticals, Inc.
Phone: 510-450-3528
Email: ir@adamaspharma.com
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