Announcement
NeuroSearch announces breakthrough tesofensine results from clinical Phase IIb
study in obesity (“TIPO-1”)
- Average weight loss of 12.6% and 11.2%, respectively, seen in the two highest
dose groups after 24 weeks treatment with tesofensine
NeuroSearch has concluded a Phase IIb Proof-of-Concept and dose finding study
(“TIPO-1”) with its drug candidate tesofensine for the treatment of obesity with
very positive results. Data from the study in 203 patients show that 24 weeks'
treatment with 0.25 mg, 0.5 mg and 1 mg tesofensine resulted in a dose-dependent
average weight loss of 6.5%, 11.2% and 12.6%, respectively (against a weight
loss of 2.0% in the placebo group). In all treatment groups, the primary
endpoints were met with high statistical significance (p < 0.0001).
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| TIPO-1 results | Placebo | Tesofensine | Tesofensine | Tesofensine |
| | | 0.25 mg | 0.5 mg | 1.0 mg |
--------------------------------------------------------------------------------
| ITT* population | 52 | 52 | 50 | 49 |
--------------------------------------------------------------------------------
| Mean weight | 103.2 | 101.7 | 100.1 | 101.3 |
| at base line | | | | |
| (kg) | | | | |
--------------------------------------------------------------------------------
| Average relative | 2.0% | 6.5%** | 11.2%** | 12.6%** |
| weight loss | | | | |
--------------------------------------------------------------------------------
| Average absolute | 2.2 | 6.7** | 11.3** | 12.8** |
| weight loss (kg) | | | | |
--------------------------------------------------------------------------------
* All patients enrolled in the study (ITT = Intention to treat)
** Statistically significantly different from placebo (p < 0.0001)
Secondary end-points, including relative change (reduction) in BMI (Body Mass
Index (kg/m2)) as well as feeling of satiety and appetite were also met (p <
0.0001 for BMI). In the two highest dose groups (0.5 mg and 1.0 mg), treatment
with tesofensine led to an average reduction in the patients' BMI of 4.
Further, results from the TIPO-1 study showed that tesofensine has a good safety
profile and was well tolerated. The most frequently reported adverse events were
mostly mild to moderate, and included dry mouth, sleep disturbances, nausea,
constipation and diarrhoea. In line with tesofensine's pharmacological profile,
there was a tendency towards an increased number of adverse event observations
in the highest dose groups (0.5 mg and 1.0 mg). A similar pattern was observed
when measuring cardiovascular effects, with slight increases in heart rate and
blood pressure. However, no clinically relevant cardiovascular adverse events or
changes in either blood pressure or pulse were seen, according to FDA criteria.
The number of patients discontinuing the study was 42 (21%) which was lower than
expected (33%). The highest numbers of patients discontinuing were observed in
the placebo group and in the highest dose group (1.0 mg).
Conclusions from the TIPO-1 study
The results of the TIPO-1 study show a clear dose-dependent weight reducing
effect of tesofensine with a marked and clinically relevant effect already at
the lowest dosing (0.25 mg).
The placebo adjusted weight loss of approx. 10% seen in both of the two highest
dose groups (0.5 mg and 1.0 mg) is highly superior to the efficacy of any
marketed drug for obesity management. The strong effect in both the low and the
middle dose combined with a generally well-tolerated high dose leaves a highly
promising therapeutic window for tesofensine.
The combined clinical safety data base from five individual studies with
tesofensine now counts approximately 1,000 patients exposed to relevant
therapeutic doses. This safety backing together with the breakthrough
weight-loss results from the TIPO-1 study as well as weight-loss data from
previous clinical studies support the preparation for a pivotal clinical Phase
III programme with tesofensine for the treatment of obesity with a clear
guidance for final dosing regimes.
Flemming Pedersen, CEO of NeuroSearch, commented:
“We are very excited about these robust results, which demonstrate that
tesofensine holds promising potential to be leading the next generation of drugs
that can offer a more efficacious and safe medical option in the struggle
against obesity. Bearing from this, tesofensine may also offer a preventive
treatment of other serious conditions relating from obesity such as type 2
diabetes. Tesofensine is a result of NeuroSearch's dedicated drug development
efforts and we are very pleased to be able to announce a major step forward in
bringing this novel product to the market.”
Professor, MD, Dr.Med.Sci. Arne Astrup***, Head of Department of Human Nutrition
at University of Copenhagen Faculty of Life Sciences, who was leading the Danish
multi-centre TIPO-1 study of tesofensine, commented:
”Current anti-obesity medications on the market produce a weight loss that is
3-5 kg greater than placebo over 6 months, and the major pharmaceutical
companies have for several years been struggling to develop drugs that produce a
6-8 kg weight loss. Therefore, I was thrilled to see that the tesofensine trial
actually produced a weight loss of approx. 10 kg more than placebo, without
major safety concerns. If tesofensine will prove to live up to this weight loss
effect in 12 months' Phase III trials, thereby opening a whole new dimension in
obesity management that can effectively compete with gastric surgery, this drug
will definitely set a new standard in obesity treatment.”
*** Conflict-of-interest statement: Professor, MD, Dr.Med.Sci. Arne Astrup is
principal investigator in the TIPO-1 study and chairman of NeuroSearch's
Scientific Advisory Board for this programme. NeuroSearch pays a fee for these
services. Arne Astrup has informed NeuroSearch that he holds 452 shares in
NeuroSearch.
TIPO-1 - Study design
The TIPO-1 Phase IIb Proof-of-Concept study was conducted as a parallel-group,
double-blind, placebo-controlled study in five centres in Denmark including a
total of 203 patients with obesity. Selection criteria in the study were a BMI
of 30-40 and an age between 18 and 65 years. Patients were randomly selected to
receive daily treatment of 0.25 mg, 0.5 mg or 1.0 mg tesofensine or placebo. The
treatment period was 24 weeks with a two weeks' lead-in and an eight weeks'
follow-up period. From the beginning of the lead-in period and until the end of
the follow-up period, all patients in the study followed the same
reduced-calorie diet and the same exercise programme.
Ongoing tesofensine studies (TIPO-2 and TIPO-4)
NeuroSearch is also conducting a human metabolic study with tesofensine
(“TIPO-2”), to evaluate the drug candidate's direct effect on metabolic
parameters such as insulin, glucose and cholesterol levels. The TIPO-2 study was
initiated in November 2006 with planned enrolment of a total of 32 patients.
Results are expected in Q4 of 2007.
Further, in June 2007 NeuroSearch initiated an open-label Phase II extension
study, TIPO-4, with tesofensine, offering all patients having concluded 24
weeks' treatment in TIPO-1 with tesofensine or placebo another six months of
treatment. In TIPO-4, the dosing of tesofensine is 0.5 mg daily for all patients
with the possibility to increase to 1.0 mg daily according to tolerance and
efficacy. The aim of TIPO-4 is continuously to evaluate tesofensine's safety
profile and tolerability as well as to generate additional observations on
maintenance of effect (weight reduction) for a total of up to 12 months. The
patients in TIPO-4 will follow the same diet and exercise programme as in
TIPO-1. To date, almost 90% of the patients having completed TIPO-1 have chosen
to continue tesofensine treatment in TIPO-4. Results from TIPO-4 are expected in
the 1st half of 2008.
The results from the TIPO-1 Phase II Proof-of-Concept study with tesofensine
does not change NeuroSearch's financial expectation for 2007 of a loss in the
range of DKK 230-250 million before recognition of associates and other equity
interests.
Asger Aamund
Chairman of the Board
Conference call
NeuroSearch will host a conference call today, 17 September 2007 at 2:00 p.m.
Copenhagen time (8:00 a.m. Eastern Time) to discuss the results from the TIPO-1
study with tesofensine. Participating in the call will be CEO Flemming Pedersen,
Chief Medicinal Officer Dieter Meier and VP, Director of IR & Corporate
Communications Hanne Leth Hillman. The conference call will be conducted in
English and can be accessed by dialing +44 (0)20 7162 0025. Prior to the
conference call, a powerpoint-presentation will be available at NeuroSearch's
website www.neurosearch.com.
Contact persons:
Flemming Pedersen, CEO, phone: +45 4460 8214 or +45 2148 0118
Hanne Leth Hillman, Vice President, Director of Investor Relations & Corporate
Communications, phone: +45 4460 8212 or +45 4017 5103
Tesofensine background
Tesofensine is a triple monoamine re-uptake inhibitor, i.e. a compound that
blocks the re-uptake of the neurotransmitters serotonin, dopamine and
nor-adrenaline in the brain with no direct effect on the monoamine receptors.
The mechanism of action behind this class of compounds is very well described.
Serotonin, dopamine and nor-adrenaline are all involved in the brain's central
regulation of food intake, metabolic control and in subsequent weight control.
Tesofensine's relative impact on the three monoamine systems is believed to
induce weight reduction through both a reduction in appetite and an effect in
the metabolic centre in the brain leading to increased thermogenesis.
NeuroSearch has conducted a preclinical study with tesofensine in Diet Induced
Obese (DIO) rats showing that tesofensine elicits a sustained weight-loss of
approximately 10%. This compares favourably to the maximal effect of
approximately 8% and 4% observed with sibutramine (Reductil®) and rimonabant
(Acomplia®), respectively, which have been used as reference compounds in the
study. The weight reduction induced by tesofensine involved a clinical relevant
loss of both abdominal and subcutaneous fat stores. Furthermore, a strong
reduction in blood cholesterol and triglycerides was observed after chronic
treatment with tesofensine. Importantly, also the insulin sensitivity was found
to be significantly increased in the animals treated with tesofensine,
suggesting a better regulation of glucose metabolism in obese and diabetic
animals.
Obesity - clinical condition
Obesity is characterised by severe excess weight in the form of fat and is
defined on the basis of a measure referred to as Body Mass Index (BMI). A BMI of
more than 30 is referred to as clinical obesity, while a BMI of between 25 and
30 expresses overweight. According to the World Health Organization (WHO),
obesity has reached epidemic proportions globally, with up to 1.6 billion adults
(over 15 years old) overweight and at least 400 million of them clinically
obese.
According to the American Obesity Association (Obesity Fact Sheet), patients
with obesity are at risk of developing one or more serious medical conditions,
which can cause poor health and premature death. Obesity has been found to be
the largest environmental influence on the prevalence of diabetes and it
complicates the management of type 2 diabetes by increasing insulin resistance
and glucose intolerance, which makes the medical treatment for type 2 diabetes
less effective. Approximate 90% of individuals with type 2 diabetes are reported
to be overweight or obese. In addition, obesity increases the risk of
cardiovascular disease, and is a major risk factor for heart attack. Over 75 per
cent of hypertension cases are reported to be directly attributed to obesity. A
weight loss of as little as 5 per cent can reduce high blood sugar and blood
cholesterol.
NeuroSearch (NEUR) is a Scandinavian biopharmaceutical company listed on the OMX
Nordic Exchange Copenhagen A/S. Our 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 part of the company's
activities are partner financed through a broad alliance with GlaxoSmithKline
(GSK) and collaborations with among others Abbott and Astellas. The drug
pipeline comprises 11 clinical (Phase I-III) development programmes: ACR16 in
Huntington's disease (in preparation for Phase III), tesofensine in obesity/type
2 diabetes (Phase II), NS2359 in depression (Phase II) and ADHD (Phase II) in
partnership with GSK, NS1209 in epilepsy and pain (Phase II), ABT-894 in ADHD
(Phase II) and pain (Phase II) in partnership with Abbott, ACR16 in
schizophrenia (Phase I) in partnership with Astellas, ACR325 in bipolar disorder
(Phase I) and ABT-107 as well as ABT-560 for the treatment of various CNS
diseases - both (Phase I) in collaboration with Abbott. In addition, NeuroSearch
has a broad portfolio of preclinical drug candidates and holds equity interests
in several biotech companies.
NeuroSearch announces breakthrough tesofensine results from clinical Phase IIb study in obesity (“TIPO-1”)
| Source: NTG Nordic Transport Group A/S
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