Dexpramipexole in ALS
Seeking to Improve the Lives of Patients with ALS
Knopp's most advanced R&D program is the development of dexpramipexole, a novel, oral investigational treatment for amyotrophic lateral sclerosis (ALS). ALS is a devastating disease of progressive paralysis with very limited treatment options.
In a Phase 2 study, dexpramipexole showed trends toward improvement in both survival and functional decline. A statistically significant result was observed in a prespecified exploratory endpoint known as the Combined Assessment of Function and Survival (CAFS), a joint rank analysis of functional outcomes adjusted for mortality. Adverse events noted in the trial included falls, muscle weakness, post-lumbar puncture syndrome, and headache, with no trend in differences in frequency among dose groups. Infrequent, reversible neutropenia was also observed.
Following our Phase 2 program, we licensed dexpramipexole for late-stage development and commercialization to Biogen Idec, which conducted large, Phase 3 trial in ALS. The Phase 3 study to meet all prespecified endpoints while demonstrating that dexpramipexole was generally well tolerated, with a safety profile similar to that seen in Phase 2.
A post hoc analysis of the Phase 3 data demonstrated that significant differences existed in the populations studied in Phase 2 and Phase 3 in certain important baseline characteristics.1 In particular, the Phase 3 trial enrolled significantly fewer subjects with a baseline diagnosis of "definite ALS," enrolled subjects with a significantly longer duration of ALS symptoms, and included a significantly greater number of patients receiving riluzole. Further analyses of the subpopulations defined by these inter-study differences showed trends toward improvement in functional decline and survival similar to those observed in Phase 2.
Knopp expects to report the results of its post hoc subgroup analyses and its next steps in the development of dexpramipexole in ALS in the second half of 2013.
1Cudkowicz et al. American Academy of Neurology. March 2013.
Knopp's pipeline consists of investigational drug products that have not been approved by the U.S. Food and Drug Administration. These investigational drug products are still undergoing clinical study to verify their safety and effectiveness.