Similar to the phase 2 MoveDMD trial, the phase 3 POLARIS trial will share the same patient population and functional endpoints.
Coming on the heels of the successful phase 2 MoveDMD trial update, which exhibited a substantially slowed disease progression with edasalonexent in patients with Duchenne muscular dystrophy (DMD), Catabasis Pharmaceuticals announced plans to further assess the drug as a treatment for DMD patients with its phase 3 POLARIS trial.
In an exclusive comment to Rare Disease Report®, Jill Milne, PhD, co-founder and chief executive officer of Catabasis Pharmaceuticals, stated, “Edasalonexent has the potential to treat all patients with DMD regardless of mutation. In the MoveDMD trial, edasalonexent substantially slowed progression of disease based on assessments of physical function and on biomarkers associated with muscle health.”
Edasalonexent is an oral small molecule inhibitor of NF-kB that helps improve skeletal, diaphragm, and cardiac disease as observed in DMD mouse and dog models. The inhibitor was developed to be beneficial to all boys affected by the disorder, regardless of mutation type.
The NF-kB pathway is the critical link between loss of dystrophin and disease manifestation and progression in those with DMD. The updated data included reports regarding new NF-kB inhibition biomarker results, which further support the significant NF-kB biomarker results observed in phase 1 of the MoveDMD trial as they are consistent with significantly decreased C-reactive protein (CRP) with edasalonexent treatment.
“Edasalonexent’s safety profile is favorably differentiated from the typical profile associated with the corticosteroid standard of care in Duchenne,” added Dr Milne. “We also believe edasalonexent has the potential to benefit the heart, which is important because cardiomyopathy still remains a leading cause of mortality in patients with Duchenne.”
By further assessing the safety and efficacy of edasalonexent in DMD patients, the randomized, double-blind, placebo-controlled POLARIS DMD trial will aim to provide support for commercial registration of the drug.
Similar to the phase 2 MoveDMD trial, the phase 3 POLARIS trial will share the same patient population and functional endpoints. One hundred and twenty-five patients with DMD, regardless of mutation mute, who are between 4 and 7 years of age and have not been on steroids for at least 6 months, are anticipated to enroll in the study. Eligibility may also be granted to boys who are on a stable dose of eteplirsen.
A change in the North Star Ambulatory Assessment score after 12 months of treatment with edasalonexent compared with placebo will serve as the primary efficacy endpoint. The age-appropriate timed function tests time to stand, 4-stair climb, and 10-meter walk/run will serve as the key secondary endpoints. In addition, assessments of growth, cardiac, and bone health will be included as additional, important criteria.
“Our phase 3 trial is designed to be very similar to our phase 2 MoveDMD trial with the same patient population and including many of the same endpoints,” clarified Dr Milne. “The phase 3 POLARIS DMD trial will have a 1-year placebo period with the North Star Ambulatory Assessment as the primary endpoint.”
For every boy administered the placebo in the phase 3 trial, 2 boys will be administered edasalonexent. After 12 months, all boys are anticipated to receive edasalonexent in an open-label extension.
Considering edasalonexent’s historically safe and strong 45-patient-years performance, which boasts muscle function preservation and substantial slowing of disease progression as well as potential skeletal muscle, diaphragm, and heart benefits, Dr Milne anticipates positive results.
“We are expecting top-line results in Q2 2020,” she added, “and with positive results, our plan would be to file for approval with the FDA as soon as we can, following the results.”
To date, the trial is expected to commence in the second half of 2018; top-line results are expected in the second quarter of 2020.