BioWorld Today Correspondent

The European Medicines Agency (EMA) has emulated the FDA in telling NeuroSearch A/S that it needs to conduct another Phase III trial of its Huntington's disease drug Huntexil (pridopidine, ACR16) before it can file for approval.

The FDA passed on the news two months ago, at an end-of-Phase II meeting with Ballerup, Denmark-based NeuroSearch. The London-based EMA did so this week in the form of scientific advice. "It was not a big surprise," NeuroSearch CEO Patrik Dahlen told BioWorld Today. "It was pretty much expected given the feedback we already got from the FDA."

It's more than a year since NeuroSearch blindsided investors by reversing the outcome of its 26-week Phase III European MermaID study. Because of a flawed statistical analysis – based on the mistaken inclusion of an adjustment for differences in patients' genetic disposition to clinically progress – the company had originally communicated that the trial reached statistical significance even though it did not.

The 12-week U.S. Phase IIb HART trial, which reported later last year, also failed to demonstrate statistical significance. The primary endpoint in each study was a change in baseline function, based on the modified Motor Score (mMS), a subscale of the Unified Huntington's Disease Rating Scale Total Motor Score (TMS).

A subsequent meta-analysis of the pooled dataset from the two studies showed that Huntexil did attain statistical significance at weeks 12 and 26 when using the TMS assessment, whereas it only attained significance according to the mMS measure at week 26. (See BioWorld Today, Jan. 4, 2011.)

"I think they really would like to see a new study with TMS as a primary endpoint; that's clear," Dahlen said. Asked why that measure was not used at the outset of the program, Dahlen, who replaced Flemming Pedersen as CEO last September, replied: "That I do not know. Decisions were made four years ago, and now here we are."

NeuroSearch aims to combine feedback from both the FDA and the EMA into a single program. It will communicate what it plans to do before the end of the present quarter. In terms of size, the new trial "will be in the same neighborhood" as the MermaiHD study, which recruited around 440 patients.

"It will not be double that; that's for sure. It may be slightly more than that," Dahlen said.

The new study will take between 12 and 18 months to complete, meaning that an approval for Huntexil – the first in a new drug class, which NeuroSearch calls dopaminergic stabilizers – is unlikely to happen before 2013 at the earliest.

In January the firm announced a major restructuring and cost reduction plan that included a 20 percent cut in staff numbers and the spinout of its discovery research into a separate unit, as it marshaled resources for the final push to go it alone on commercializing Huntexil. (See BioWorld Today, Jan. 12, 2011.)

Shares in NeuroSearch (COPENHAGEN:NEUS) closed Tuesday at DKK49.10 (US$9.28), down 5.6 percent.