MedDay recently disclosed full study results from the MS-SPI and MS-ON Phase 2b/3 trials of its therapeutic candidate MD1003 in patients with multiple sclerosis (MS). Specifically, the trials included people with “not active” progressive MS and those with either relapsing or progressive MS and visual loss, respectively. Data, presented at the recent American Academy of Neurology 2016 Annual Meeting in Vancouver, Canada, demonstrated better efficacy in reversing disease progression than a drug has previously achieved in not-active progressive MS.
MD1003 is a pharmaceutical formulation of high-dose biotin, a type of vitamin B. The drug, which is already commercially available in certain European countries under early access programs, has previously shown efficacy in patients with progressive MS. It acts in MS by increasing a route of cellular energy production, protecting against the breakdown of nerve cell axons. It also activates enzymes that are setting the pace on myelin repair by being involved in the production of myelin constituents.
The MS-SPI trial, focusing on not-active progressive MS, a difficult-to-treat form of the disease, explored the effects of MD1003 in 103 patients, compared to 51 others who received placebo during 12 months. The study continued in a 12-month extension phase, during which all patients received the drug but remained uninformed of whether they had been treated with MD1003 in the first phase.
MS-SPI met its primary endpoint — the proportion of patients who improved on either the Expanded Disability Status Scale (EDSS) or a timed walk test. MedDay reported improvement in 12.6 percent of patients after nine months, confirmed at 12 months, and equivalent to a reversed progression. During the same period, none of the placebo-treated patients improved.
During the extension phase, patients who had been on MD1003 from the start continued improving, with 13.2 percent of them demonstrating less disability at 18 months, and 15.4 percent at 24 months.
“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,” Professor Ayman Tourbah at CHU de Reims, France, and the studies’ principal investigator, said in a press release. “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.”
Meanwhile, the MS-ON study included patients both with relapsing-remitting (RR) MS and progressive disease. The group consisted of 64 RRMS patients having a fixed visual loss after an acute inflammation of the optic nerve, and with 31 patients with progressive visual loss. During its first phase, running for 24 weeks, 65 patients received MD1003, and 28 received placebo. The first part was followed by an additional study period of 24 weeks, during which all patients received the active drug.
The study found that patients treated with MD1003 improved their eyesight slightly more than placebo-treated patients, but the difference was not statistically significant. Further analysis revealed that only the patients with progressive disease benefited from the treatment.
The studies also demonstrated good safety and tolerability data for MD1003.
“When we compare these results to other trials in progressive MS that involved more than 6000 patients overall, this is clearly the best effect size ever observed. 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. 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,” Professor Tourbah said.
“Taken together, these studies are very promising and provide hope for a condition that has thus far been largely intractable using treatments targeting neuroinflammation,” added Professor Bruce Cree at University of California, San Francisco, and the principal investigator in the prospective U.S. study of MD1003. “That the extension study from the SPI trial showed an apparent durability of effect suggests that high dose biotin may have disease-modifying properties in addition to its proposed role in enhancing energy metabolism.
“Furthermore, the positive impact of high dose biotin points to a new line of inquiry in understanding the pathophysiology of progressive MS,” Professor Cree concluded.