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The press release below involves a correction to previously announced results of the Huntexil (ACR16) clinical trial in Europe.
In February, Neurosearch announced that there was a statistically significant difference between the treatment and control groups in the primary endpoint, the Modified Motor Score of the United Huntington's Disease Rating Scale. Probability was reported as .02 meaning that the likelihood of these results being a chance variation rather than a meaningful treatment difference is less than 1 in 50.
Today they announced that they had adjusted for CAG counts in their original analysis (but had not disclosed this). They found faster progression as the CAG count increased. Including the CAG count as a variable in the analysis resulted in the probability of .02.
Once that adjustment was removed from the analysis, however, p = .0425. A probability of .05 or less would normally be acceptable; however, since this study involved two treatment groups, p needed to be .025 or less for the results to be considered statistically significant.
This means that the results look promising but are not conclusive and that an additional Phase III study is likely to be necessary before Neurosearch can apply for approval.
Neurosearch should have been clear that they had made such an adjustment in reporting the results for the primary endpoint of the study. In addition, they still do not have all of the CAG counts of participants so the adjustment was a preliminary one.
We will continue to follow up and report information as it becomes available.
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
28 April 2010 - Announcement
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
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):
PP (Per Protocol) population:
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:
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.
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.
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