Knopp Neurosciences to initiate Phase 3 studies of KNS-760704 in AL

In an invited presentation today before the annual meeting of the American Academy of Neurology, Knopp Neurosciences Inc. ("Knopp") described further encouraging trends observed in a previously reported Phase 2 study of KNS-760704 (dexpramipexole) in ALS.

“Despite the limited sample size and treatment periods, ongoing review of the Phase 2 data shows consistently encouraging trends in both pre-specified and post hoc analyses”

Knopp reported that post hoc analyses showed a significant, dose-dependent trend of reduced treatment failure, as measured by both the ALS Functional Rating Scale-Revised ("ALSFRS-R") and forced vital capacity, over the 12-week, placebo-controlled portion of the study.

• In the case of ALSFRS-R, the number of treatment failures, defined as the loss of 6 points or greater in ALSFRS-R scores from baseline, totaled 9 subjects (or 33%), in the placebo group; 8 subjects (35%), in the 50 mg/day group, 4 subjects (15%) in the 150 mg/day group, and 2 subjects (8%) in the 300 mg/day group>
• In the case of pulmonary function, the number of treatment failures, defined as a reduction in forced vital capacity of 20% or greater from baseline, totaled 8 subjects (30%) in the placebo group, 3 subjects (13%) in the 50 mg group, 3 subjects (12%) in the 150 mg group, and 1 subject (4%) in the 300 mg group>

Knopp emphasized that these encouraging trends require confirmation in the large, long-term, controlled Phase 3 study setting necessary to establish that the drug is both safe and effective for ALS patients. Nevertheless, the additional analyses reported today were concordant with trends previously reported from Knopp's Phase 2 study, which suggested the potential for dexpramipexole to improve outcomes in both function and survival.

"Despite the limited sample size and treatment periods, ongoing review of the Phase 2 data shows consistently encouraging trends in both pre-specified and post hoc analyses," said Merit Cudkowicz, M.D., Professor of Neurology at the Massachusetts General Hospital of Harvard Medical School, who served as the principal investigator in the trial and who presented the Knopp study results by invitation at the Academy's 2010 Clinical Trials Plenary Session. "We are eager to initiate Phase 3 studies as soon as protocol development and other arrangements are completed."

As previously reported, the two-part Phase 2 study found that dexpramipexole met its primary objective in assessing its safety and tolerability in ALS patients for up to nine months. Secondary objectives included measuring the clinical effects of dexpramipexole on functional decline and mortality. The two-part design of the study provided the opportunity to assess the effects of the drug in the same sample of ALS subjects in two randomized, double-blind treatment periods separated by a one-month placebo washout.

In Part 1 of the study, 102 subjects received daily doses of 50 mg, 150 mg, or 300 mg of dexpramipexole or placebo for 12 weeks. As previously reported, dexpramipexole showed a dose-dependent trend in slowing the rate of disease progression as measured by the difference in slopes of the ALSFRS-R across treatment groups, with the greatest benefit observed in the 300 mg dose group.

In Part 2 of the study, 92 subjects were re-randomized to receive daily doses of 50 mg or 300 mg of dexpramipexole for 24 weeks. In addition to results again suggesting a dose-dependent trend in slowing the rate of disease progression as measured by the ALSFRS-R, there was also a trend toward a survival benefit in the 300 mg group compared with the 50 mg group. In an exploratory test comparing subject rankings on the basis of mortality and functional outcomes, subjects in the 300 mg group had a significantly improved outcome compared with the 50 mg group.

Knopp expects to initiate Phase 3 studies of dexpramipexole in ALS before the end of 2010.