Knopp Biosciences' Dexpramipexole Meets Primary Endpoints in Phase 2 Trial Results in Hypereosinophilic Syndromes (HES)

Knopp Biosciences LLC  announced on 5/10/18 the publication of a report in the journal Blood that a Phase 2 study of dexpramipexole in hypereosinophilic syndromes (HES) met its co-primary endpoints.

A team of investigators led by Dr. Amy Klion at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), undertook the open-label study of dexpramipexole as a steroid-sparing agent in subjects with HES. Dexpramipexole had been observed to produce a significant, targeted reduction of peripheral blood eosinophils in earlier clinical trials in amyotrophic lateral sclerosis.

The trial enrolled 10 subjects and met the co-primary endpoints of: 1) percentage of subjects experiencing a ≥50% reduction in MED and 2) reduction of glucocorticoid requirement among all subjects. Notably, three of the four responders meeting the primary endpoint exhibited complete hematological responses (eosinophil count of zero or near-zero) and were able to discontinue prednisone completely. These subjects have remained symptom-free, eosinophil-free, and steroid-free for 13-32 months while continuing dexpramipexole treatment, as reported in the article.

The investigators also reported that three of four responders who underwent biopsies had complete resolution of eosinophilia in affected skin or gastrointestinal tissue. Delayed and partial hematological responses were also noted in the trial.

Dexpramipexole was well tolerated, with no adverse events leading to drug interruption or discontinuation.

HES comprises a heterogeneous group of rare disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. The NIH trial enrolled subjects with the FIP1L1-PGDFRA-negative form of the disease, which accounts for 85-90% of all HES. Although glucocorticoid therapy is the first-line treatment for patients with FIP1L1-PGDFRA-negative HES, many patients develop serious side effects or resistance over time.
The Phase 2 study was conducted as part of an agreement between Knopp Biosciences and NIAID, demonstrating industry-government collaboration in the field of rare disease drug development.