Catabasis Pharmaceuticals is facing challenges in its efforts to develop Edasalonexent (CAT-1004) — an oral drug that targets NF-kB, a protein activated in Duchenne muscular dystrophy (DMD) — to treat the rare degenerative disease.
Edasalonexent is being evaluated in MoveDMD, an ongoing Phase 1/2 clinical trial (NCT02439216) consisting of three parts that looks at the drug’s safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) in 31 boys ages 4 to 7 with DMD, compared to a placebo drug.
Part A of the trial is finished, and all the drug dose levels were well-tolerated with no major safety signals reported. Yet as Catabasis reported in January, Part B did not meet its primary efficacy endpoint, which was improvement in lower leg muscle function by magnetic resonance imaging (MRI). Secondary endpoints included the 10-meter walk/run, a four-stair climb, and the time it takes boys to stand, as well as scores from the North Star Ambulatory Assessment — a functional scale specifically designed for ambulant boys affected DMD.
Two distinct doses of the drug were tested over a 12-week period: 67 mg per kg of body weight a day and 100 mg/kg a day. But after 12 weeks of treatment, there were no statistically significant alterations between edasalonexent treatment groups (67 mg/kg/day and 100 mg/kg/day) and a placebo on lower-leg muscle function as seen in MRI.
Furthermore, while boys in the edasalonexent 100 mg/kg/day treatment group had improvements across multiple timed function tests and the North Star Ambulatory Assessment, compared to boys treated with a placebo drug, these changes were not statistically significant. Also, the 67 mg/kg/day treatment group had mixed results compared with both the 100 mg/kg/day groups and the placebo, also not achieving statistical significance.
The company also reported on the ongoing Part C open-label extension of MoveDMD, which is evaluating the long-term safety and efficacy of edasalonexent. Boys taking part in Part C are receiving the drug for 36 weeks beyond the study’s 12-week placebo-controlled portion of the study. All primary and secondary endpoints are being monitored, with results from Part C expected this year, an interim update by the middle of this year.
“Looking forward in 2017, Part C of the MoveDMD trial will allow us to collect data for up to 48 weeks of treatment and provide important information about dose and activity with extended duration, as well as endpoints for possible future clinical trials of edasalonexent,” Catabasis CEO Jill C. Milne said in a press release. “Following additional data analysis from Part C, we will determine the next steps for edasalonexent in DMD. Catabasis is also moving the development of our rare disease pipeline forward, with advances in CAT-5571 for cystic fibrosis and CAT-4001 for neurodegenerative diseases including Friedreich’s ataxia and ALS.”
Meanwhile, Catabasis published two articles in two top journals. The first, “Disease-modifying effects of orally bioavailable NF-κB inhibitors in dystrophin-deficient muscle”, appeared in JCI Insight and reported positive preclinical data of edasalonexent showing that treatment ameliorated the dystrophic process in DMD mouse models.
The second study, “A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects,” appeared in the Journal of Clinical Pharmacology.
This paper reported the results of randomized, double-blind, single-ascending-dose study (NCT01440166) that assessed the safety, pharmacokinetics and pharmacodynamics of single or multiple edasalonexent doses up to 6000 mg in 52 healthy adults. This was the first-in-human study showing that edasalonexent was safe, well tolerated, and useful in inhibiting muscle degeneration.
The U.S. Food and Drug Administration has granted edasalonexent orphan drug, fast track and rare pediatric disease designations for the treatment of Duchenne, which affects about 1 in 3,500 male births. The European Commission has similarly granted Edasalonexent orphan medicinal product status to treat DMD.