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Neurosearch Reports Good Results from the
European Trial of ACR16
Neurosearch has reported positive results from the MermaiHD study, the European Phase III study with Huntexil® (pridopidine) in Huntington's disease. The HD community knows this drug by its original designation of ACR-16.
Huntexil (ACR16) is a small molecule belonging to a pharmacological class called dopamine stabilizers. It can enhance or inhibit activity depending on the initial level. In other words, if dopamine activity levels are too high, Huntexil can decrease them, but if activity is too low, Huntexil can increase it. This contrasts with neuroleptics where a reduction in activity of this neurotransmitter occurs, regardless of initial level.
"For the 30,000 people in the U.S. currently affected by Huntington's disease, this is exciting news," said Louise Vetter, Chief Executive Officer of the Huntington's Disease Society of America. "Loss of motor function is just one of the devastating aspects of HD, and the potential for a new treatment to improve this function has direct impact on the quality of life and health of everyone impacted by this disease."
"It is important to recognize that this news is the direct result of active participation in clinical studies to evaluate the potential of Huntexil (ACR16). In the U.S., the HART study for ACR16 has been underway for more than a year and unfortunately, enrollment is slow. We hope that with good news like this, more families see the value of being a part of a clinical research," added Ms. Vetter. "Without clinical trial participation by community members, exciting therapies like Huntexil will not be able to stand for FDA approval."
THE NEUROSEARCH PRESS RELEASE
NeuroSearch Announces Positive Top-line Results From Phase III Huntexil(R) Study in Huntington's Disease (the MermaiHD Study
-- Huntexil(R) significantly improves motor functions in Huntington patients
-- Positive effects observed on both voluntary and involuntary motor symptoms
-- Huntexil(R) was very well tolerated with an adverse event profile similar to placebo
COPENHAGEN and BALLERUP, Denmark, Feb. 3, 2010 (GLOBE NEWSWIRE) -- NeuroSearch (NEUR) today reported positive top-line results from the MermaiHD study, the European Phase III study with Huntexil(R) (pridopidine) in Huntington's disease.
The MermaiHD study met the primary endpoint to show an effect on voluntary motor function. In addition, data from the 437 Huntington patients, who participated in the study (= ITT population) show that six months' (26 weeks) treatment with Huntexil® results in significant improvements in a broader range of voluntary and involuntary motor symptoms associated with the disease. The study was conducted in 32 centers across Europe, and showed a very high compliance with 92% of the patients completing the study and 82% in full compliance with the study.
Treatment with Huntexil® 45 mg BID (twice daily) demonstrated statistically and clinically significant improvements compared to placebo in the ITT population on the following measures of motor symptoms in Huntington's disease.
Symptoms scale Significance level Description
Modified Motor ITT: p <0.02 The mMS is the primary efficacy
Score, mMS measure of the MermaiHD study,
and assesses voluntary motor
function as part of the TMS
Total Motor ITT: p <0.001 The TMS is the motor part of the
Score, TMS Unified Huntington's Disease
Rating Scale (UHDRS) and
measures overall motor effects
including both voluntary and
involuntary motor symptoms
Eye Movements ITT: p <0.002 Eye movements are voluntary
movements but not included in
Dystonia ITT: p <0.001 Dystonia is part of the
involuntary motor symptoms and
included also in the TMS
[explanation of charts from Marsha Miller:]
On the primary endpoint on the Modified Motor Score which assesses voluntary motor function, the experimental group receiving 45 mg twice daily improved significantly compared to the placebo group (p <.02).
The Modified Motor Scale is part of the Total Motor Scale which is the motor part of the Unified Huntington's Disease Rating Scale (the UHDRS), a standard assessment of the disease's effects on movement, including both voluntary and involuntary motor symptoms. The experimental group receiving 45 mg twice daily improved significantly compared to the placebo group (p <.001).
The experimental group receiving the higher dosage also improved on dystonia (prolonged muscle contraction resulting in twisting body motions) which is also measured in the TMS (p < .001). They also improved in voluntary eye movements which is not part of the TMS (p < .002)
Treatment with Huntexil® 45 mg QD (once daily) showed some improvements on these motor function domains, however the improvements at this lower dosage did not reach statistical significance.
The improvements in motor function observed with Huntexil® 45 mg twice daily in the MermaiHD study appear very robust, as they (1) remain consistent across assessments and analyses, (2) show increasing separation from placebo over time, and (3) are consistent also across the two pre-stratified study groups of patients on use/non-use of antipsychotic medication; approximately 40% of patients were on antipsychotics. The importance of studying both patient groups has been emphasized by experts and regulators to demonstrate that Huntexil® improves the symptoms of Huntington's disease per se, and that it is also safe in patients treated with antipsychotics. The use of antipsychotics showed no influence on the positive treatment effects of Huntexil®.
In the study, Huntexil® was generally very well tolerated with an adverse event profile similar to placebo, and the results show no indication that treatment with Huntexil® would be associated with worsening of disease signs and symptoms.
Following the results, NeuroSearch is now initiating interactions with scientific advisors and regulatory agencies (EMEA and FDA) to discuss the MermaiHD study outcome and the plans for submissions for market authorisation for Huntexil® as a novel treatment for Huntington's disease.
Principal investigator, Prof. Justo García de Yébenes, Hospital Ramon y Cajal, Madrid, Spain, commented, "Huntington's disease is a progressive disorder with motor, cognitive, and behavioral symptoms. Huntexil® is the first medication to have demonstrated an overall improvement of the motor impairment in Huntington patients with no worsening of other signs or symptoms and without compromising patient safety. Overall, the MermaiHD study results show that Huntexil® has a favorable clinical risk/benefit profile, and I believe it could be useful to many of my patients."
Chairman of the European Huntington's Disease Network, EHDN, Prof. G.B. Landwehrmeyer, commented, "The EHDN is very proud to have been part of making the MermaiHD study a success both in terms of quality and time. With more than 400 patients participating, the trial is one of the largest so far conducted in Huntington's disease in Europe, and recruitment was completed within one year. I would like to thank all participants and their caregivers, all investigators and their staff as well as the employees at the EHDN for their dedicated contribution to this achievement."
Flemming Pedersen, CEO of NeuroSearch, commented, "The Phase III results from the MermaiHD study are very encouraging, demonstrating that Huntexil® can provide significant benefits to Huntington patients on symptoms not reached by any current treatment, and this without any "trade-offs" in terms of safety or worsening of any other disease symptoms. We remain determined to bring Huntexil® forward as a new medication to patients with Huntington's disease and we will work closely with physicians and regulatory authorities to make this happen as soon as possible."
NeuroSearch is also evaluating Huntexil® in a second randomised and placebo-controlled study, the HART study, conducted in the USA and Canada and in approximately 220 patients with Huntington's disease. Patient recruitment in the HART study is still ongoing, and study results are expected in the second half of 2010.
Also, the MermaiHD study is followed by an open-label treatment period, which is still ongoing. Patients, who completed the six months' randomised study treatment, have been offered to continue open-label treatment with up to 45 mg Huntexil® twice daily for six months. Close to 90% of the patients have chosen to continue treatment in the open-label phase, and the last patient is expected to complete the full 12 months treatment period in May 2010. Results from the open-label treatment period are also expected to be available in the second half of 2010.
For more information about the U.S. trial, click here: Clinicaltrials.gov
A list of participating sites can be found here: HART participating sites