Published: 2010-04-28 09:43:26 CEST
NeuroSearch 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

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

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

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
• 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

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
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

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

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