Experimental MS treatments
Experimental MS treatments
Research continues on possible treatments to add to the existing spectrum. Safety and efficacy are still being established.
Long-term safety data of MD1003 (high dose pharmaceutical grade biotin) in the MS-SPI trial were presented . Results from the open-label extension phase (OLE; month 12-48) indicated that biotin was well-tolerated, with no new safety signals. Among the 133 patients who entered the extension phase, 49% were still receiving treatment after 48 months. The main reasons for treatment withdrawal in the extension phase were lack of efficacy and withdrawal of consent. Adverse events (AEs) were experienced by 78% vs. 88% of patients in the treatment and placebo groups, respectively. Serious AEs were experienced by 35% vs 36% of patients. Progressive MS relapse rate did not appear to be influenced by MD1003.
Evobrutinib (M2951) is the first inhibitor of Bruton’s tyrosine kinase (BTK) that demonstrated reduction of disease activity in relapsing MS . In the presented trial, participants were randomised to evobrutinib 25 mg once-daily (QD), 75 mg QD, 75 mg twice-daily (BID), open-label dimethyl fumarate (240 mg BID; reference arm), or placebo for 48 weeks. Placebo-treated patients transitioned to evobrutinib 25 mg QD after 24 weeks. Among 261 patients, the number of Gd+ T1-lesions were significantly reduced with evobrutinib 75 mg QD (P=0.002) and 75 mg BID (P=0.03) vs placebo in weeks 12–24. Annualised relapse rate (ARR) decreased over 24 weeks at both evobrutinib doses. ARR over 48 weeks was 0.25 and 0.11 for evobrutinib 75 mg QD and 75 mg BID, respectively (see Figure). The sum of new or enlarging T2 lesions in weeks 12–24 was reduced in the evobrutinib 75 mg BID group vs placebo (P=0.02). Evobrutinib was well-tolerated; the most common treatment-emergent AEs were nasopharyngitis and reversible, asymptomatic liver enzyme elevations.
Figure: Annualised relapse rate at weeks 24 and 48 (modified intention-to-treat population) 
The novel monoclonal antibody ublituximab targets a unique epitope on the CD20 antigen and is glyco-engineered for enhanced B cell depletion through antibody-dependent cellular cytotoxicity (ADCC). In the OLE of the phase 2 trial TG1101-RMS201, 1-hour infusions of ublituximab continued to be safe and well-tolerated in relapsing MS patients . The 45 OLE participants received 450 mg ublituximab infusions every 24 weeks for 96 weeks. B cells were efficiently depleted in most patients within 24 hours of receiving the first dose of ublituximab. A median B cell depletion of >99% was observed at week 4, and maintained at week 24 and 48. At week 48, ARR was 0.07, with 93% of subjects being relapse-free and 74% fulfilling NEDA criteria. Not a single Gd-enhancing T1 lesion was detected at week 24 or 48 (P=0.003). AEs possibly related to ublituximab were infrequent during the extension phase. Infusion related reactions (all grade 1 or 2) occurred in 4 patients (9%).
- De Seze J, et al. EAN 2019, EPO3200.
- Montalban X, et al. EAN 2019, O1205.
- Fox E, et al. EAN 2019, O4107
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