NeuroSearch Falls as Troubled Huntexil Raises Safety Concern
By Cormac Sheridan
NeuroSearch A/S's task of securing backing for an additional Phase III trial of its Huntington's disease drug, Huntexil (pridopidine), has gotten a bit more difficult, following the release of data from a multiple-ascending-dose trial indicating that the compound causes QT interval prolongation in healthy volunteers.
Huntexil – the first in a new drug class that NeuroSearch calls dopaminergic stabilizers – had not been administered previously to Huntington's patients at doses beyond 90 mg twice daily. The present trial was designed to investigate the safety and tolerability of the drug at higher doses. However, it never attained a planned dose of 112.5 mg twice daily, due to tolerability issues observed at 90 mg twice daily, including the appearance of psychiatric signs and symptoms.
Moreover, the incidence, severity and duration of adverse events, such as nausea, headache, dizziness and vomiting increased at higher dose levels. And doses of both 67.5 mg twice daily and 90 mg twice daily caused QT interval prolongation that was above the clinical-concern threshold.
"It's a very weak signal, but it's there," Karin Garre, executive vice president and chief development officer at Ballerup, Denmark-based NeuroSearch, told BioWorld International.
The effect at 45 mg twice daily also was greater than that seen in earlier trials. Although some degree of QT prolongation was seen in earlier trials, "it was not of clinical concern," she said.
QT interval prolongation, which can be associated with severe and even fatal cardiac arrhythmias, has derailed plenty of drug development programs before now. That the signal has only been picked up at this late stage in the drug's development – Huntexil already has been the subject of extensive Phase III and Phase IIb trials – will raise eyebrows among potential partners.
Normally, any such issues would be picked up in earlier trials, if not in preclinical development. "It's true," Garre acknowledged.
The new findings will be incorporated into the design of the upcoming, second Phase III trial of Huntexil, which will be called PrimeHD, although NeuroSearch will review the data further before communicating its precise plans, Garre said. The company, which reported DKK144 million (US$24.3 million) in cash on March 31, needs to either raise additional investment or secure a partnering deal to undertake the planned second Phase III trial.
The company also said it is implementing "appropriate safety measures" in the ongoing open-label phase of its U.S. Phase IIb HART trial and in its European compassionate use program, each of which employs a 45-mg twice daily dose.
Although the news was unexpected, it does provide greater clarity for the program, Garre said. "Now we know what it looks like and can move on."
The Nasdaq OMX market was closed due to a public holiday Monday when NeuroSearch disclosed the news. However, the company's stock (COPENHAGEN:NEUR) dropped more than 14 percent Tuesday, to reach DKK6.34 by early afternoon, having closed Friday at DKK7.40.
It's the second piece of bad news to hit the company of late. Last week, NeuroSearch disclosed that the Danish financial regulator had filed charges against the company for alleged share price manipulation, under the Danish Securities Trading Act.
The charges arise from the company's Feb. 3, 2010, disclosure of data from the Phase III trial of Huntexil, which, due to a flawed statistical analysis, erroneously stated that the study hit its primary endpoint of improving voluntary motor function.
The company's share price rose 97 percent in response. (See BioWorld International, Feb. 10, 2010.)
Several weeks later, however, the company amended the disclosure and concluded that the study had not attained the primary endpoint after all. NeuroSearch has denied any wrongdoing, and the company said it is cooperating with the authorities. (See BioWorld International, May 5, 2010.)
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