Catabasis Pharmaceuticals Inc. (NASDAQ:CATB) shares tumbled 70.7 percent lower to $1.18 by Wednesday's market close as top-line data from a proof-of-concept trial of its Duchenne muscular dystrophy (DMD) candidate edasalonexent (CAT-1004) showed that 12 weeks of treatment with the NF-kB inhibitor failed to significantly impact a biomarker indicative of benefits in lower leg muscle composition and inflammation in boys with the fatal condition. Next steps for Catabasis will turn on interim results from an ongoing open-label extension of the trial, a readout of which is expected during the second quarter.

The most recent readout comes from part B of the Cambridge, Mass.-based company's MoveDMD trial, a 12-week, randomized, double-blind placebo-controlled study designed to test the safety and efficacy of edasalonexent in 31 boys ages 4 to 7 years old affected by DMD. It followed the conclusion of part A of the study, which found all three doses of edasalonexent tested were generally well tolerated with no safety signals observed.

For part B, investigators used magnetic resonance imaging T2 (MRI T2) as the primary endpoint because previous studies conducted with steroids showed short-term changes in MRI T2 measures of leg muscles and long-term benefits on functional test in patients affected by Duchenne. The hope at Catabasis was that the measure could be an early biomarker that would allow the company to see an effect of edasalonexent at just 12 weeks of treatment.

The primary efficacy endpoint of average change from baseline to week 12 in the MRI T2 composite measure of lower leg muscles for the pooled edasalonexent treatment groups of 67 mg/kg/day and 100 mg/kg/day compared to placebo was not met (0.37 milliseconds for the pooled edasalonexent treatment groups vs. 0.47 milliseconds for placebo). A smaller increase in MRI T2 correlates with less of an increase in muscle inflammation.

The 67 mg/kg/day treatment group had mixed results compared with both the 100 mg/kg/day treatment group and placebo, which in each case were not statistically significant, the company said.

While the edasalonexent 100 mg/kg/day treatment group consistently showed numerical improvement vs. placebo across multiple measures, the changes were not statistically significant. Nonetheless, Catabasis CEO Jill Milne told investors during a conference call that "we believe these results warrant further evaluation to see if the signal strengthened in longer term data from the ongoing open-label extension."

Among the longer-term data points the company will assess are measures like fat fraction and time function test; the latter of which could potentially be used as a primary endpoint for a phase III trial.

The results soured Cowen and Co. analyst Phil Nadeau's take on the company's prospects, moving him to lower a $30 target on company shares to just $4.04 on Tuesday. The "results are not strong enough to provide us confidence that edasalonexent is reasonably likely to have a path to market and, without a placebo arm in the [open label extension], we think strong signals are unlikely to develop," he wrote.

Edasalonexent is a SMART (Safely Metabolized And Rationally Targeted) linker conjugate of salicylic acid and the omega-3 fatty acid docosahexaenoic acid, or DHA, a naturally occurring unsaturated fatty acid with anti-inflammatory properties. Catabasis designed it to inhibit NF-kB, a protein that is activated in DMD and that drives inflammation, fibrosis and muscle degeneration, and suppresses muscle regeneration.

The program's stumble is far from uncommon in the DMD space. Sarepta Therapeutics Inc.'s DMD drug Exondys 51 (eteplirsen) gained accelerated approval in September 2016 only after enduring a tumultuous travail. And, despite regulatory success in Europe, PTC Therapeutics Inc. drew a refuse-to-file letter from the FDA for its entrant in the field, Translarna (ataluren). Santhera Pharmaceuticals Holding AG failed to win an accelerated approval bid for its candidate, Raxone (idebenone). (See BioWorld Today, Sept. 20, and Oct. 18, 2016)

Milne said that her team will now complete and present the full analysis of the MoveDMD trial at upcoming scientific conferences this year. It will also continue to monitor the boys on edasalonexent in the open label extension portion of the trial looking to see if early signals strengthen in the longer term data.