- Trial 006 demonstrated a statistically
significant and clinically meaningful reduction in OFF-time and
increase in proportion of patients “ON” by 8:00 am (primary and key
secondary endpoints) -
NeuroDerm Ltd. (Nasdaq:NDRM), a clinical stage pharmaceutical
company developing drug-device combinations for central nervous
system (CNS) disorders, today announced that a preliminary analysis
of trial 006 demonstrated that the trial successfully met its
primary, key secondary and additional secondary endpoints. Trial
006 was an international open label, blinded rater, phase II study
of ND0612H, NeuroDerm's high dose continuous, subcutaneously
delivered levodopa/carbidopa (LD/CD) liquid formulation, in
patients with advanced Parkinson's disease.
NeuroDerm also announced that it has modified
its EU clinical and regulatory development strategy following a
meeting with the European Medicines Agency (EMA). The modified
strategy will be based on NeuroDerm's restarted and amended iNDiGO
phase III efficacy study (trial 007), rather than on bioequivalent
pharmacokinetic (PK) studies. Based on discussions with the EMA,
NeuroDerm believes that this strategy should allow it to pursue a
broader EU label, with no effect on its clinical and regulatory
timelines.
“The very prominent responder effect, as well as
the significant reductions in OFF-time and troublesome dyskinesia
observed in trial 006, are extremely encouraging and demonstrate
the substantial potential for ND0612 to make a meaningful
difference in the lives of patients living with Parkinson’s
disease,” said Oded S. Lieberman, PhD, CEO of NeuroDerm. “We
believe that restarting and amending the iNDiGO trial,
incorporating both an ND0612H arm and new endpoints that reflect
these very positive preliminary results from trial 006, should
support a broader label in the EU and increase the clinical and
commercial potential of ND0612 while not affecting our clinical
timelines. We are committed to improving the lives of
Parkinson's patients by achieving our clinical and regulatory
objectives as quickly as possible and providing Parkinson’s disease
patients with a safer and more effective alternative to current
treatment options.”
Trial 006 EndpointsThe primary
endpoint of this study was to assess the change from baseline to
day 28 in daily OFF-time (normalized to 16 waking hours) as
assessed by a blinded rater. A key secondary endpoint was to
assess the percentage of subjects who were “ON” by 8:00am and
9:00am. Additional secondary endpoints were also evaluated as well
as safety and tolerability.
Trial 006 DesignTrial 006 was a
28-day multicenter, international (US, EU and Israel),
parallel-group, blinded rater, randomized phase II study that
investigated the efficacy, safety, tolerability and
pharmacokinetics of two dosing regimens (R1 and R2) of ND0612H and
compared them to the baseline of standard optimized oral
therapy:
- R1: 24 hour administration of ND0612H (720/90mg LD/CD) at a
high day rate for 18 hours and a low night rate for 6 hours.
- R2: 14 hour administration of ND0612H during the waking hours
(538/68mg LD/CD) complemented by a morning dose of 150/15mg oral
LD/CD.
All patients could add oral LD/CD therapy at any
time as needed. The trial enrolled 38 patients with advanced
Parkinson’s disease.
Trial 006 Preliminary ResultsThe 38 enrolled
subjects had typical characteristics for patients with advanced
Parkinson’s disease including: an average age of 63.5 years, 11.5
years since diagnosis and an average baseline OFF-time of 5.3 hours
per day.
OFF-time (primary endpoint):The primary endpoint
was met in R1. From 5.5 hours at baseline, the OFF-time was reduced
by 2.8 hours (p equals 0.004). There was a smaller,
non-statistically significant reduction of 1.3 hours in OFF-time in
R2.
“ON” by 8:00am and 9:00am (key secondary
endpoint):In R1, the proportion of patients who achieved the first
“ON” by 8:00am (as reported by the patient) increased from 11% at
baseline to 50% by day 28 (p equals 0.020), and, by 9:00am, from
26% at baseline to 75% (p equals 0.004). In R2, dosing began in the
morning and there was therefore no improvement from baseline at
either timepoint.
Complete reduction of OFF-time (post-hoc
analysis):In R1, 42% of patients had a complete reduction in
OFF-time to zero hours (in R2, 11% experienced complete resolution
of OFF-time). Patients who experienced reduction in OFF-time
(greater than 0 hours change) during the trial were defined as
“Responders” and constituted 68% of all patients (12 patients in R1
and 14 patients in R2). Eight (66%) of the Responders in R1 (and
two (14%) of the Responders in R2) experienced a complete reduction
of their OFF-time to zero hours; all Responders in R1 experienced a
reduction of more than 50% in their OFF-time.
“Good” ON (secondary endpoint):Good ON
(defined as “ON” with no or mild dyskinesia, as assessed by the
blinded rater) increased in R1 from 9.2 hours by 3.7 hours (p less
than 0.001), and in R2 from 8.5 hours by 2.8 hours (p equals
0.003).
Unified Parkinson’s Disease Rating Scale (UPDRS) III by 8:00am
(post-hoc analysis):UPDRS III score by 8:00am decreased in R1 from
37.4 at baseline by 19.1 points (p less than 0.001) and from 37.3
at baseline by 10.7 points in R2 (p equals 0.001).
Troublesome Dyskinesia (post hoc
analysis):Troublesome dyskinesia (defined as “ON” with moderate or
severe dyskinesia as assessed by the blinded rater) decreased from
5.1 hours at baseline by 3.5 hours (p equals 0.011) in the subgroup
of all patients who had at least 1 hour of troublesome dyskinesia
at baseline (N equals 14, R1 and R2 combined).
Oral LD Dosing and Frequency (post hoc
analysis):Average dosing frequency of oral levodopa decreased in
all patients from 6.6 times at baseline to 2.3 times per day by day
28. The average dose of oral LD decreased from approximately1100mg
at baseline to approximately 330mg.
Safety and Tolerability:33 subjects (87%) out of
38 completed the study with 5 who did not complete the study, two
of which were due to adverse events: one due to an infection at the
infusion site and the other due to worsening of symptoms. Infusion
site reactions (nodules, bruising and erythema) were common yet
generally well tolerated. These results corroborate the safety and
tolerability data obtained in previous studies and did not raise
new safety or tolerability concerns.
Preliminary Results:Preliminary trial 006
results demonstrate that the R1 dosing regimen provides a
significant reduction in OFF-time and a significant increase in
ON-time with no or mild dyskinesia. A substantial percentage of
subjects experienced complete resolution of OFF-time. The treatment
was associated with some nodules, consistent with prior trials, but
otherwise did not raise new safety or tolerability concerns.
Benefits were also seen with the R2 regimen in spite of the study
design whereby patients started levodopa therapy later in the
morning. ND0612H devices were generally found to be reliable
with only few minor, correctable malfunctions reported. No
inconvenience related to the wearing of the device was reported for
either day or night administration.
Detailed trial results will be presented at a
future medical meeting.
ND0612 EU Clinical and Regulatory
DevelopmentNeuroDerm recently received minutes from a
meeting held in January 2017 with the EMA's Scientific Advice
Working Party. Based on this meeting and on the preliminary
results of trial 006, NeuroDerm has modified its EU clinical and
regulatory development path. Upon completion of its ongoing trials,
NeuroDerm plans to submit a marketing application based on the
results of an amended iNDiGO phase III efficacy study and the
ongoing BeyoND (trial 012) long-term safety trial, seeking to
obtain a broader label for ND0612 than the label that could have
been granted under a PK regulatory route in the EU. The
previously planned PK trial (trial 009) will not be carried
out. Anticipated timelines for submission of the EU marketing
application remain unchanged. NeuroDerm's U.S. clinical and
regulatory development timelines also remain unchanged.
iNDiGO TrialNeuroDerm's iNDiGO
phase III efficacy study (trial 007) will be restarted and amended
to support a broad label claim in the EU for ND0612. The trial will
be expanded from 150 to 240 patients by adding a third treatment
arm of ND0612H to the current ND0612L and control arms.
Furthermore, new endpoints that reflect the recent trial 006
results, including a responder analysis, will be incorporated into
this trial. NeuroDerm believes that these should enable the company
to seek approval for both the low- and high-dose versions of ND0612
in the EU. It is anticipated that iNDiGO will be completed in
2018, in parallel to the ongoing long term BeyoND safety trial
(Trial 012).
Conference Call Details
NeuroDerm will host a conference call at 8:30 a.m. ET today.
Individuals can access the webcast in the Events and Presentations
section of the Company’s website, by clicking here, or by dialing
844-452-2810 (U.S.) or 574-990-9831 (outside of the U.S.).
The passcode is 79280228. A webcast will be archived on the
website.
About ND0612ND0612 is designed
to significantly reduce motor complications in Parkinson's disease
patients through continuous, subcutaneous delivery of LD/CD
solution. Previously completed Phase II trials demonstrated that
the low dose ND0612L maintained steady, therapeutic levodopa plasma
concentrations that were associated with major changes in several
clinical parameters including “OFF” time reductions when added to
optimal oral standard of care. The high dose ND0612H, intended for
severe Parkinson’s disease patients, was shown to reach even higher
levodopa steady plasma levels, indicating that it may provide an
effective therapy alternative to current treatments requiring
surgery such as deep brain stimulation and LD/CD Intestinal
Gel.
About Parkinson's
diseaseParkinson's disease is a progressive
neurodegenerative illness characterized by reduced dopamine in the
brain, resulting in a debilitating decrease in the patient's motor
and non-motor functions. Its symptoms, such as trembling in the
extremities and face, slowness of movement and impaired balance and
coordination, worsen over time and gravely impact the patient's
quality of life. Levodopa is the most effective treatment for
Parkinson’s disease. However, chronic oral levodopa treatment is
associated with fluctuations in motor response as result of which,
despite the benefits of the drug, patients can experience periods
of impaired motor and non-motor functions, also referred to as
“OFF” time. In addition, mainly as a result of
excessive/intermittent oral doses of levodopa aimed at treating the
“OFF” time, some patients experience involuntary movements, or
dyskinesia. The “OFF” time and dyskinesia affect the majority of
levodopa-treated Parkinson's disease patients and can interfere
with day-to-day functions, causing patients to become severely
disabled. Current evidence suggests that intermittent dosing with
standard oral formulations of levodopa contributes to the
development of these motor complications. By contrast, it has been
shown that continuous administration of levodopa can effectively
treat motor fluctuations in Parkinson's disease patients without
increasing troublesome dyskinesia; however, a convenient route for
continuous administration has not been introduced to date.
About NeuroDermNeuroDerm is a
clinical-stage pharmaceutical company developing drug-device
combinations for central nervous system (CNS) disorders that are
designed to overcome major deficiencies of current treatments and
achieve enhanced clinical efficacy through continuous, controlled
administration. NeuroDerm has three product candidates in different
stages of development which offer a solution for almost every
Parkinson’s disease patient from the moderate to the very severe
stage of the disease. NeuroDerm has developed a line of levodopa
and carbidopa (LD/CD) product candidates administered through small
belt pumps that deliver a continuous, controlled dose of LD/CD. The
LD/CD product candidates are ND0612L and ND0612H, which are used
for treatment of moderate and advanced Parkinson’s disease
patients, respectively, and which are delivered subcutaneously. In
addition, NeuroDerm is developing ND0701, a novel subcutaneously
delivered apomorphine formulation for patients who suffer from
moderate to severe Parkinson’s disease and who do not respond well
to LD/CD. NeuroDerm is headquartered in the Weizmann Science Park
in Rehovot, Israel.
Forward-Looking StatementsThis
press release contains forward-looking statements, within the
meaning of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995, Section 27A of the Securities Act of
1933, as amended, and Section 21E of the Securities Exchange Act of
1934, as amended that involve risks and uncertainties. Such
forward-looking statements may include projections regarding our
future performance and may be identified by words like
"anticipate," "assume," "believe," "continue," "could," "estimate,"
"expect," "intend," "may," "plan," "potential," "predict,"
"project," "future," "will," "seek" and similar terms or phrases.
The forward-looking statements contained in this press release are
based on management's current expectations and projections about
future events. There are important factors that could cause our
actual results, levels of activity, performance or achievements to
differ materially from the results, levels of activity, performance
or achievements expressed or implied by the forward-looking
statements. In particular, you should consider the risks provided
under "Risk Factors" in our annual report on Form 20-F for the year
ended December 31, 2015 filed with the Securities and Exchange
Commission. Any forward-looking statement made by us in this press
release speaks only as of the date hereof. Factors or events that
could cause our actual results to differ may emerge from time to
time, and it is not possible for us to predict all of them. We
undertake no obligation to publicly update any forward-looking
statements, whether as a result of new information, future
developments or otherwise.
NeuroDerm Contact:Oded S. Lieberman, PhD,
CEOoded@neuroderm.comTel.: +972-8-946 2729; Cell: +1-617-517
6077
U.S. Investor Contact:David CareyLazar Partners
Ltd.dcarey@lazarpartners.com+212-867-1768
U.S. Media Contact:Erich SandovalLazar Partners
Ltd.esandoval@lazarpartners.com+917-497-2867
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