NeuroSearch announces publication in The Lancet of tesofensine Proof-of-Concept results from TIPO-1

- Tesofensine can produce weight loss twice that of currently approved obesity
drugs 

NeuroSearch announces publication in The Lancet of the results from a Phase II
Proof-of-Concept study, TIPO-1, of its anti-obesity compound, tesofensine. 

Tesofensine can produce a weight loss twice that of currently approved obesity
drugs, and should be studied in Phase III trials. These are the conclusions of
an article published early Online and in an upcoming edition of The Lancet
written by Professor Arne Astrup, Department of Human Nutrition, Faculty of
Life Sciences, University of Copenhagen, Denmark, and colleagues. 

Increased obesity prevalence worldwide, in both developed and developing
countries, results in more people with cardiovascular disease, diabetes,
musculoskeletal disorders and cancer. Whilst gastric bypass surgery
substantially reduces bodyweight and obesity-related disease, the researchers
believe a treatment gap exists between the effectiveness of currently marketed
obesity drugs and gastric-bypass surgery. Tesofensine - which inhibits the
presynaptic uptake of the neurotransmitters noradrenaline, dopamine and
serotonin in the brain - has been shown to be safe and effective in animal
models. It also caused unintended weight loss when it was given obese patients
with Parkinson's or Alzheimer's disease when it was researched for those
conditions. The drug works by suppressing hunger, leading to an energy deficit,
which burns off excess body fat. 

Tesofensine was investigated in a randomised, placebo-controlled Phase II
study, named TIPO-1, in five Danish obesity management centres, involving 203
obese patients, weighing a mean of just over 100 kg at baseline (body mass
index 30-40 kg/m2). The patients were prescribed a limited-energy diet and
assigned to tesofensine 0.25 mg (52 patients), 0.5 mg (50 patients), 1.0 mg (49
patients) or placebo (52 patients), all once daily for 24 weeks. The primary
outcome was percentage change in bodyweight. A total of 161 patients completed
the study, and mean weight loss recorded for placebo and diet was 2.2 kg and
for tesofensine 0.25 mg, 0.5 mg and 1.0 mg was 6.7 kg, 11.3 kg, and 12.8 kg
respectively. For the 0.5 mg and 1.0 mg doses, this represented a weight loss
around twice that attained using sibutramine (Reductil®/Meridia®) or rimonabant
(Accomplia®), the currently-approved therapies in Europe - and in half the
treatment time. Blood pressure was increased in the 1.0 mg group. The most
common side-effects caused by tesofensine were dry mouth, nausea, constipation,
hard stools, diarrhea and insomnia. 

The authors conclude that the 0.5 mg dose of tesofensine is more promising than
the 1.0 mg dose because it produces a similar weight loss with less
side-effects. They say: “We conclude that tesofensine 0.5 mg, once daily for 6
months, has the potential to produce twice the weight loss as currently
approved drugs; however, larger Phase III studies are needed to substantiate
our findings.” 

Professor Arne Astrup says*):
”The results indicate that obese patients who typically obtain a weight loss of
3-5 kg with existing drugs on the market, can now expect a weight loss of 10 kg
with tesofensine alone. If, in addition, the treatment is combined with the
right diet, the total weight loss can amount to 20 kg." 
*) Arne Astrup owns 966 shares in NeuroSearch. 

Flemming Pedersen, CEO of NeuroSearch, comments:
“We are very pleased to see our TIPO-1 results published in The Lancet and with
 firm suggestion that tesofensine has a superior profile as a new treatment
within weight management and that such a treatment offering is strongly needed.
Tesofensine has been studied in more than 1,000 patients at relevant
therapeutic doses, and we are highly satisfied with the efficacy and safety
profile of the drug. Following the outstanding weight loss results from the
TIPO-1 Proof-of-Concept study, we have reported interim results from a 48-week
extension study showing a placebo-controlled average weight loss of 13 kg after
48 weeks of treatment with tesofensine. This is almost tripple the effect seen
with existing anti-obesity drugs and even comparable to the weight loss effect
of surgical procedures such as gastric by-bass.” 

NeuroSearch has succesfully completed all Phase III preparatory work with
tesofensine and expects to initiate pivotal studies with the drug. 


Contact persons: 

Arne Astrup, Professor, Department of Human Nutrition, University of
Copenhagen, Denmark, telephone:  +45 3533 2476 or +45 2143 3302 

Flemming Pedersen, CEO, telephone: +45 4460 8214 or +45 2148 0118

Hanne Leth Hillman, Vice President, Director of IR & Corporate Communications,
telephone: +45 4460 8212 or  +45 4017 5103 



NeuroSearch (NEUR) is a Scandinavian biopharmaceutical company listed on Nasdaq
OMX Copenhagen. 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 CNS disorders. A substantial share of its activities is
partner financed through a broad alliance with GlaxoSmithKline (GSK) and
collaborations with, among others, Abbott and Astellas. NeuroSearch's drug
pipeline comprises 14 clinical (Phase I-III) development programmes: ACR16 for
Huntington's disease (Phase III), tesofensine for obesity and in Type 2
diabetes (Phase III in preparation), NS2359 for depression (Phase II) and ADHD
(Phase II) in partnership with GSK, ABT-894 for ADHD (Phase II) and pain (Phase
II) in partnership with Abbott, ACR16 for schizophrenia (Phase I) in
partnership with Astellas, ACR325 for Parkinson's disease (Phase II in
preparation) and bipolar disorder (Phase II in preparation), ABT-107 and
ABT-560 for the treatment of various CNS disorders - both (Phase I) in
collaboration with Abbott, NSD-644 for pain (Phase I) in partnership with GSK,
ACR343 for Parkinson's disease (Phase I) and NSD-788 for anxiety/depression
(Phase I). In addition, NeuroSearch has a broad portfolio of preclinical drug
candidates and holds equity interests in several biotech companies.