Dive Brief:
- Results newly in from the Part C open label extension of MoveDMD, the Phase 2 study of Catabasis Pharmaceuticals' edasalonexent, show positive impacts on decline of muscle function over 24 and 36 weeks in boys aged 4 to 7 years.
- The rate of decline of muscle function slowed substantially compared with an earlier part of the Phase 2 study that showed the drug was no better than placebo.
- The next step will be a Phase 3 trial of edasalonexent in DMD regardless of mutation type, with topline results expected in 2020. Catabasis shares have shot up by 43% since Monday.
Dive Insight:
"We are extremely excited to see edasalonexent change the trajectory of disease in the MoveDMD trial with substantially slowed disease progression," said Jill Milne, CEO of Catabasis.
Edasalonexent is an oral small molecule that inhibits NF-kB, a protein that drives inflammation, fibrosis and muscle degeneration.
While these results are positive, earlier data were negative. The Part B results did not meet the primary efficacy endpoint at either the lower or higher dose. There were treatment-associated effects at 12 weeks in the higher 100 mg/kg/day treatment group, but these weren’t statistically significant. The failed results in the earlier, blinded part of the study routed the company's stock. The earlier results were no doubt the more important part of the study, but Catabasis is using this glimmer of hope to move into later stages.
The next step for the drug's development is a single global Phase 3 trial planned for next year.
"The Phase 3 trial will enroll around 125 boys aged four to seven, and its design and clinically relevant endpoints have had regulatory input from the FDA," Jill Milne told BioPharma Dive in an interview. "This is the younger side of the Duchenne muscular dystrophy population, and here the population is more homogeneous as it is the age before many receive treatments such as steroids. We believe our mechanism of action allows an earlier intervention where it can have a greater effect."
Catabasis will begin recruitment in the first half of 2018, and will file a New Drug Application after the topline results in 2020.
"While it can be harder to recruit in rare disease populations, we don't foresee problems as there are fewer studies in this age group, and our mechanism of action is agnostic to mutations, unlike PTC Therapeutics' Translarna and Sarepta's Exondys51. Our Phase 2 study enrolled within a quick timeframe," the CEO said.
Translarna (ataluren) is already approved on a conditional basis in Europe, but is struggling to gain a OK from the Food and Drug Administration. Meanwhile, Exondys51 gained a controversial approval in the U.S. Milne sees plenty of room for another therapeutic, which because of its mode of action could actually expand the market.
"Ours works across all mutations, compared with Translarna and Exondys51, which each work in subsets of the DMD population. We also see it as having potential as a foundation therapy in combination with the exon-skipping approaches," she added.
Last year, Catabasis teamed up with Sarepta Therapeutics to combine Sarepta's exon-skipping drugs with Catabasis' oral NF-kB inhibitor. Pre-clinical data from this work, which shows increased dystrophin in the MDX mouse model as a result of treatment with edasalonexent in combination with an exon-skipping modality is being presented at the 22nd International Congress of the World Muscle Society this week.
At the time of the agreement, Milne described the combination as making "mechanistic sense" because the NF-kB inhibitor could further boost levels of dystrophin. The location of the companies just two blocks apart in Cambridge, Mass. also helps logistically.
The open-label segment of MoveDMD allows patients who are amenable to exon 51 skipping treatment to receive Exondys51 along with edasalonexent, and the first eligible patient has started treatment.