Danish English
Published: 2010-04-28 09:43:26 CEST
NTG Nordic Transport Group A/S
Company Announcement
NeuroSearch A/S announces the results of additional assessment and analysis of data from the Phase III MermaiHD study with Huntexil® in Huntington's disease
- Further assessment of data from the study shows that the significance
value
for the primary study endpoint, the modified Motor Score (mMS) of p=
0.042 did
not meet the pre-specified level of p< 0.025. With inclusion of the
clinically
relevant CAGn adjustment, the p-value is < 0.02 as previously
communicated 

- This revised statistical conclusion is isolated to the
primary endpoint, and
there are no changes to the previously communicated
results for other endpoints 

- Overall, the data confirm that Huntexil® has
a unique and clinically
meaningful effect on global motor function in
Huntington's patients with a good
safety profile 

- The regulatory strategy
for Huntexil® is unchanged, and NeuroSearch will
initiate dialogue with
regulatory authorities based on the MermaiHD study
results 


Copenhagen,
28 April 2010 - NeuroSearch (NEUR) has completed additional data
assessment
and analyses of the MermaiHD study, a European Phase III study with
Huntexil®
in Huntington's disease. 

Overall, the additional assessments and analyses
confirm the clinical top-line
results as previously communicated in
Announcement no. 01-10 on 3 February
2010, namely that 

• Huntexil®
significantly improves motor function in Huntington patients
• Huntexil®
demonstrates positive effects on both voluntary and involuntary
motor symptoms

• Huntexil® was very well tolerated with an adverse event profile similar
to
placebo 

The conclusion regarding the primary endpoint, the mMS with a
significance
level of p< 0.02, which was communicated as part of the top-line
results, was
based on a clinically relevant baseline covariate adjustment for
differences in
patients' genetic disposition, i.e. the length of CAG repeats
(CAGn) in the
diseased gene sequence. This adjustment is judged to be
clinically important
and appropriate in ensuring a more meaningful
representation of the data set.
Based on this assessment, the primary endpoint
for the MermaiHD study was
concluded to be met (p< 0.025). 

The adjustment
for individual differences in patients' CAGn x treatment was
pre-specified in
the study protocol as a sensitivity analysis but not as part
of the main
effects model for the primary analysis. In view of this, the
statistical
results have been re-assessed, demonstrating a formal p-value of
0.042 for the
primary endpoint, the mMS, and consequently indicating that the
study did not
rearch the p< 0.025 significance level (Bonferroni adjustment) as
pre-defined
in the study protocol. As adjustments for CAGn are recommended for
the
analysis of clinical studies in Huntington's disease, NeuroSearch will
include
the CAGn covariate adjusted analysis in the presentation of the
MermaiHD study
results to regulatory authorities. 

Overall, in the MermaiHD study, 26 weeks
treatment with Huntexil® (45 mg twice
daily) led to significant improvements
of patients motor function measured on
both mMS and TMS (the Total Motor
Score) as compared to placebo. The
statistical significance outcomes are
summarised below for both endpoints as
measured in the ITT (Intention to
Treat) population and the PP (Per Protocol)
population (the 82% of the
patients who completed the study in compliance with
the study protocol):



ITT (Intention to Treat) population 

Huntexil®(45 mg twice daily) vs
placebo	Main effects model1)  +CAGn x trt2)*
+CAGn x age3)* 
mMS	p = 0.042	p<
0.02	p< 0.01
TMS	p = 0.004	p< 0.001	p<0.001
			
PP (Per Protocol)
population:

Huntexil®(45 mg twice daily) vs placebo	Main effects
model1)	+CAGn x
trt2)*+CAGn x age3)* 
mMS	p = 0.014	p< 0.005	p< 0.005
TMS	p<
0.01	p< 0.0025	p< 0.001

1) Main effects model: ANCOVA including baseline
mMS/TMS score, neuroleptic
cotreatment and gender as covariates 
2) Main
model plus CAGn x treatment as baseline covariate 
3) Main model plus CAGn x
age as baseline covariates 
* CAG values not yet available for 44 patients (of
which13 in the placebo
group, 18 in the 45 mg once daily group and 13 in the
45 mg twice daily dose
group) 

The additional data assessment generally
confirms the consistency and
robustness of the results and supports the
overall positive clinical outcome of
the MermaiHD study, including the
following positive findings: 

• Huntexil® demonstrates a superior treatment
effect in patients with an
elevated CAGn score (considered a surrogate marker
for rate of progression and
disease prognosis) 
• The significant
improvements observed in mMS are driven primarily by positive
effects on fine
motor skills, gait and balance 
• Positive effects were also observed in
certain cognitive and functional
domains 
• Significant benefit was observed
on the independence scale in patients with
higher CAGn scores 

In the
study, Huntexil® also demonstrated a very good safety profile and was
shown to
have no significant disadvantages in terms of worsening of other
disease signs
or symptoms. The further data analysis also showed that there
were no
significant changes in vital signs between the treatment groups.


Conclusions and next steps
The revised statistics do not change the
overall clinical evidence from the
MermaiHD study demonstrating that Huntexil®
offers clinically meaningful
improvements to Huntington patients across a
broad range of motor symptoms
without worsening any other disease signs and
symptoms and thus shows promise
in being a uniquely efficacious and well
tolerated therapeutic option.
NeuroSearch continues to plan for initial
interactions with regulatory
authorities based on the results from the
MermaiHD study. 


Flemming Pedersen
CEO


Telephone
conference
NeuroSearch will conduct a telephone conference today at 10:30 am
DK time (9:30
am UK time and 4:30 am US time) in connection also with the
release of the
company's interim report for Q1 2010. Participating in the
conference will be
CEO 
Flemming Pedersen, Vice President and CFO Anita
Milland and Vice President and
Director of IR & Capital Market Relations Hanne
Leth Hillman. The conference
will be conducted in English and the dial-in
numbers are UK and International:
+44 207 509 5139, US: +1 718 354 1226, and
DK: +45 3271 4767. 


Contact persons:
Flemming Pedersen, CEO, telephone:
+45 4460 8214 or +45 2148 0118
Hanne Leth Hillman, Vice President, Director of
Investor & Capital Market
Relations, telephone: +45 4460 8212 or +45 4017 5103



About the MermaiHD study 
The MermaiHD study is a randomised,
double-blinded and placebo-controlled Phase
III study conducted at 32 clinical
centres across Europe to examine the effects
of Huntexil® on a number of
Huntington's disease parameters. The study included
437 patients with
Huntington's disease from Austria, Belgium, France, Germany,
Italy, Portugal,
Spain and the UK. 

In the study, patients were randomly allocated to receive
treatment with one of
two Huntexil® doses (45 mg. once or twice daily) or
placebo during a 26-week
period. Patients completing the randomised phase have
been offered to continue
into a 26-week open-label extension phase, in which
they receive treatment with
45 mg. Huntexil® twice daily, only. 

The
primary study endpoint is voluntary motor function in Huntington
patients,
measured on the modified Motor Score (mMS), which is defined as the
sum score
of voluntary motor items (items 4-10 and items 13-15) from the Total
Motor
Score (TMS), The TMS includes 15 items of motor assessment and comprises
the
motor part of the Unified Huntington's Disease Rating Scale (UHDRS),
including
both voluntary motor function (mMS and eye movements) and
involuntary movements
such as dystonia and chorea. TMS is also included as
endpoint in the MermaiHD
study. Other endpoints include cognitive function,
behaviour and symptoms of
depression and anxiety. 


About Huntington's
disease 
Huntington's disease is a highly disabling, hereditary
neurodegenerative
genetic disorder, which leads to damage of the nerve cells
in certain areas of
the brain including the basal ganglia and the cerebral
cortex. 

The disease has a prevalence of about 1: 10,000 in most western
countries with
an estimated 70,000 affected patients in North America and
Europe combined. In
other parts of the world, the disease prevalence varies
substantially among
geographic regions and is generally lower. The total
number of patients outside
North America and Europe is estimated to be in the
range of 30,000 to 35,000. 

Patients with Huntington's disease experience a
wide variety of symptoms
typically grouped into three categories: motor,
cognitive and psychiatric
symptoms. The onset of symptoms is typically around
35 and 45 years of age, and
patients hereafter deteriorate gradually with a
life expectancy of 10 to 20
years. 

Eventually every person with
Huntington's disease will require full-time care.
Huntington's disease
represents high unmet medical needs, as there is currently
no cure or
effective treatment available and only a limited number of novel
drugs in
development. 


NeuroSearch - Company profile
NeuroSearch (NEUR) is a
Scandinavian biopharmaceutical company listed on NASDAQ
OMX Copenhagen A/S.
The company's core business covers the development of novel
drugs, based on a
broad and well-established drug discovery platform focusing
on ion channels
and central nervous system (CNS) disorders. A substantial share
of the
activities is partner financed through strategic alliances with Eli
Lilly and
Janssen and a license collaboration with Abbott. The drug pipeline
comprises
eight clinical (Phase I-III) development programmes: Huntexil®
for
Huntington's disease (Phase III), tesofensine for obesity (Phase III),
ABT-894
for ADHD (Phase II) in partnership with Abbott, ACR343 for
schizophrenia (Phase
II ready), ACR325 to treat dyskinesias in Parkinson's
disease (Phase Ib),
ABT-560 for the treatment of cognitive dysfunctions (Phase
I) in collaboration
with Abbott, NSD-788 for anxiety/depression (Phase I) and
NSD-721 for social
anxiety disorder (Phase I). In addition, NeuroSearch has a
broad portfolio of
preclinical drug candidates and holds equity interests in
several biotech
companies.
 


facade_04_beskaret.jpg
fonds.11-10 - the mermaihd study_additional results - uk - final.pdf