MedDay hails new progressive MS data as EMA filing beckons

France

French biotech MedDay has posted the full, follow-up data from two mid- to late-stage trials for its multiple sclerosis candidate, showing it has a long-term impact on reversing progression in the disease in a difficult-to-treat patient population.

The company’s data comes from two trials, with the first--the Phase IIb/III MS-SPI study--designed to assess the potential of its lead candidate MD1003 to reverse disease progression in patients with not-active progressive MS.

This particular form of the disease currently has no drug treatments on the market, with most approved therapies focusing on the relapsing, remitting forms of MS. There is a sub-group of patients, with primary progressive MS (PPMS) characterized by disease progression from onset, which affects 10–15% of MS patients.

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PPMS can be further divided into active or not-active progressive disease based on the existence or not of superimposed inflammatory activity--this represents the most difficult-to-treat population, and is the sub-population MedDay is targeting with MD1003.

The drug is thought to have a twofold effect, activating acetyl-CoA carboxylases that are the rate-limiting enzymes in the production of fatty acids required for myelin synthesis, and also activating the Krebs cycle in axons that have been demyelinated, increasing their energy supply.

Just over 100 patients were randomized to receive MD1003, with 51 having a placebo for a year, followed by a 12-month extension phase during which all patients received MD1003 but remained blinded as to whether they had received the active drug during the first phase.

The primary endpoint--which was “particularly challenging” according to the biotech--was defined as the proportion of patients with either improvement of the Expanded Disability Scale (EDSS) or TW25 (timed 25-foot walk) after nine months and confirmed at 12 months--which equates to a confirmed reversion of progression.

MedDay hit the primary endpoint, with 12.6% of patients in the MD1003 arm showing a confirmed reversion of progression, compared to none at all in the placebo arm. And when a number of patients in the placebo group were switched to MD1003 for the extension phase, the proportion of responders reached 11.9% after 2 years--showing that treatment with MD1003 reversed progression in some patients who switched to the drug.

Commenting on the first study’s results, Prof. Ayman Tourbah, the principal investigator of the studies, CHU de Reims, Department of Neurology, France, said: “Full results of the MS-SPI study are especially remarkable.  This is the first time that a drug has reversed the progression of the disease in a statistically significant proportion of patients.

“In addition, if we look at the mean Expanded Disability Scale (EDSS) change, the data compare very favorably with all previous trials that looked at the same endpoint. Almost no progression was observed in patients treated with MD1003 for 24 months and this has never been observed before.  When we compare these results to other trials in progressive MS that involved more than 6,000 patients overall, this is clearly the best effect size ever observed.”

But the results of the second study were disappointing. The MS-ON study was set up to see whether MD1003 could speed up recovery following incomplete remission of an acute relapse and/or specifically improve patients with progressive disability.

For this purpose, the study enrolled 62 patients with fixed visual loss following an acute optic neuritis in the previous three years (non-progressive chronic optic neuropathy) together with 31 MS patients showing progressive visual loss assessed at two different visits in the previous 3 years (progressive optic neuropath).

Final results showed that, overall, patients who received MD1003 improved slightly more than patients who received the placebo (average of 3.1 letters in the MD1003 arm versus 1.8 letters in the placebo arm)--but this was not statistically significance, and therefore missed its primary endpoint.

Prof. Tourbah explained: “The MS-ON trial failed to reach its primary endpoint but this is most likely due to a majority of patients with relapsing remitting MS in this trial. Indeed, if we focus on patients with the progressive chronic neuropathy phenotype, they seem to have benefited from the drug in the same way as patients in the MS-SPI trial.”

He said that results from both studies “are therefore consistent” and “point to the fact that targeting neuron and oligodendrocyte metabolism represents a promising and novel disease modifying therapy approach in progressive MS, particularly in patients with a not-active progressive disease.”

Top-line results had been announced late last year, but this is the first time it has released full details and follow-up data.

Earlier this month, the biotech raised $38.5 million in a Series B funding round, with its CEO Dr. Frédéric Sedel telling FierceBiotech that he aimed to file the drug with the EMA in the coming weeks. The company will likely have to do further trials before submitting to the FDA.

But it’s not the only company seeking an approval in the progressive space. In February, Swiss cancer specialist Roche ($RHHBY) gained an FDA “Breakthrough Status” for its MS candidate ocrelizumab for primary progressive multiple sclerosis.  

This was based on top-line, pivotal Phase III data released last year showing ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo.

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