Positive results from the pivotal phase III clinical trial, MS-SPI were presented at the American Academy of Neurology Annual Meeting.
The study demonstrated evidence of the efficacy and safety of MD1003, a highly-concentrated pharmaceutical-grade Biotin administered at a dose of 300 mg per day in the treatment of primary and secondary progressive multiple sclerosis.
The primary endpoint was met ( p=0.0051, Fisher’s exact test ) in the intent to treat population with 12.6% of patients in the MD1003 arm showing an improvement of EDSS ( Expanded Disability Status Scale ) or TW25 ( a timed 25-foot walk ) at month 9, confirmed at month 12, compared to none of the patients ( 0% ) in the placebo arm.
The primary endpoint was supported by secondary analyses showing evidence for a decrease in the risk of disease progression.
The mean change of EDSS between M0 and M12 decreased in the MD1003 group ( -0.03 ) compared to progression in the placebo group ( +0.13, p=0.015 ).
In the MD1003 arm, only 4% of patients treated with MD1003 exhibited EDSS progression at M9 confirmed at M12 versus 13% in the placebo group ( p=0.07 ), which equates to a 67% decreased risk of progression in the active arm within the studied period.
The study was not prospectively powered to reach significance for this secondary endpoint.
MD1003 was well tolerated. The overall incidence of adverse events was similar across the two groups. One patient died from suicide in the active arm, however this event was not considered as related to the drug.
In 5 patients, abnormal laboratory data indicated that MD1003 may affect the results of immunoassays which use biotinylated antibodies and substrates.
The MS-SPI study is a randomized 2:1, double-blinded, placebo-controlled study conducted in 16 multiple sclerosis reference Centres in France. Treatment duration was one year.
The patient population was defined as patients suffering from primary progressive multiple sclerosis ( PPMS ) or secondary progressive multiple sclerosis ( SPMS ) with EDSS progression in the two years prior to inclusion and with EDSS ranging from 4.5 to 7.
Patients excluded from the study included those with disease modifying therapy ( DMT ) introduced in the 3 months prior to inclusion, patients with Fampridine introduced in the month prior to inclusion, or patients with evidence of relapse or Gadolinium-MRI activity within the past year.
Patient enrolment commenced in October 2013 and was completed in January 2014 with 166 patients screened and 154 patients randomized ( 103 in the MD1003 arm and 51 in the placebo arm ).
There were no statistically significant differences in the characteristics of the patients in the two patient groups.
There were 12 treatment discontinuations in the MD1003 arm and 8 in the placebo arm. All analyses being performed according to the intent to treat ( ITT ) principle, all randomized patients were analysed according to the treatment arm they were assigned to.
The primary endpoint of the study was defined as the proportion of patients who improved at 9 months ( M9 ), with a confirmation of the improvement at 12 months ( M12 ).
Improvement was defined as either a decrease in EDSS ( by at least 1 point for baseline EDSS less than or equal to 5.5 and 0.5 points for EDSS greater than or equal to 6 ) or an improvement in TW25 ( a timed 25-foot walk ) of at least 20%.
The comparison for each outcome was the best EDSS and TW25 scores obtained at the screening and randomisation visits.
MD1003 is an investigational medicine thought to have both pro-myelinogenic effects and to enhance the supply of energy for nerve impulse transmission.
MD1003 is an active pharmaceutical ingredient administered at a dose of 300 mg /day in multiple sclerosis.
MD1003 has a mode of action which potentially influences two targets related to progressive MS: (1) it activates acetyl-CoA carboxylases ( ACC1 and ACC2 ), the rate-limiting enzymes in the synthesis of fatty acids required for myelin synthesis, and (2) it activates the Krebs cycle in demyelinated axons to increase energy production.
Multiple sclerosis is the most common disabling neurological disease among young adults, with first symptoms typically manifesting between 20 and 40 years of age. In the majority ( 85% ) of cases, patients experience an initial phase of relapsing-remitting neurological dysfunction ( RRMS ), which typically evolves into a secondary progressive disease at a later point in the clinical course ( SPMS ).
Once multiple sclerosis is in the progressive phase, individuals experience a gradual worsening of neurological disability leading to problems with vision, walking, incontinence, cognitive changes, fatigue, and pain.
Primary progressive multiple sclerosis ( PPMS ) characterized by disease progression from onset is less common, affecting 10–15% of patients.
Despite these different initial clinical phenotypes, the time to reach certain disability milestones and the ages at which the milestones are reached are similar for patients with PPMS and SPMS. Recent guidelines have therefore proposed to group PPMS and SPMS within a single entity called progressive disease. The overall prevalence of patients with progressive disease is estimated to be at least 40% of all patients with multiple sclerosis. ( Xagena )
Source: MedDay Pharmaceuticals, 2015