番茄社区

WASHINGTON -- High doses of biotin were associated with improvements in disability among patients with multiple sclerosis (MS), researchers reported here.

The MS-SPI trial met its primary endpoint, with a larger proportion of patients in the drug group achieving certain targets for reductions in Kurtzke Expanded Disability Status Scale scores or EDSS (13% versus 0%, P=0.0051) versus placebo, according to Ayman Tourbah, MD, of Centre Hospitalier Universitaire de Reims in France.

Drugmaker MedDay Pharmaceuticals announced positive results with the drug last week, but Tourbah delivered the full presentation here at the American Academy of Neurology annual meeting.

Biotin is a water-soluble vitamin that acts as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acid synthesis. It activates acetyleCoA carboxylase, which is thought to be a key enzyme in myelin synthesis.

An earlier open-label pilot study of 23 patients showed that high doses of biotin -- from 100 to 600 mg/day -- resulted in progressive and sustained improvement of disability in primary and secondary progressive MS patients.

The randomized, double-blind, multicenter placebo-controlled MS-SPI trial enrolled 154 patients from 16 sites around France who had primary or secondary progressive MS with an EDSS score of 4.5 to 7 and evidence of EDSS progression within the past 2 years.

Patients were randomized to either 300 mg/day of biotin (currently known as MD1003), and treated for 48 weeks.

The primary endpoint was the proportion of patients who improved at 9 months -- and had their improvements confirmed at 12 months -- where improvement was defined as decreased EDSS by at least 1 point for scores of 5.5 or lower, and by 0.5 points for those with an EDSS score of 6 or higher.

Tourbah and colleagues found that patients on the drug did better than those in the placebo group in both an intention-to-treat (ITT) and per-protocol analysis.

In the ITT population, about 13% of patients hit the primary endpoint, compared with none of the placebo patients (P=0.0051), and for the per-protocol population, about 15% of drug patients hit the primary endpoint compared with none of the placebo patients (P=0.0093).

Additional analyses also found a significantly greater overall improvement in EDSS scores for those on the drug compared with those on placebo (-0.03 versus 0.13, P=0.014).

Proportions of adverse events were similar in both groups, although there was an increase in hyperthyroidism in the drug groups, developing in 5% of patients compared with none in the placebo group. Tourbah said going forward, this should be monitored and, if approved, clinicians should have a strategy for dealing with this complication in place.

There was also one suicide in the drug group, compared with none in the placebo group, but the researchers determined that this was unlikely to be due to drug treatment.

, on Mount Sinai Hospital in New York City, who was not involved in the study, noted that change in EDSS was indeed small, and it was a small proportion of patients who hit the prespecified improvements.

"It is hard to call it a successful 'phase III' trial with the primary endpoint being achieved by 13 people," Krieger told 番茄社区. "That said, improvement of any sort is a high efficacy bar to hit, and I definitely think it merits replication in a truly phase III-size trial, with imaging and other confirmatory endpoints."

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