A significantly higher percentage of patients treated with ublituximab compared to those on teriflunomide achieved no evidence of disease activity status.
Results from the phase 3 ULTIMATE 1 & 2 studies (NCT03277261; NCT03277248) showed that ublituximab (TG Therapeutics) significantly reduced annualized relapse rate (ARR) and magnetic resonance imaging (MRI) parameters compared to teriflunomide (Aubagio; Sanofi) in patients with relapsing forms of multiple sclerosis (RMS).1,2
The data were presented at 7th Congress of the European Academy of Neurology and will support a biologics license application (BLA) submission expected in the third quarter of 2021.
The ULTIMATE 1 (n = 673) and ULTIMATE 2 (n = 660) studies evaluated the safety and efficacy of 1-hour, 450-mg infusion of ublituximab every 6 months, following the Day 1 infusion of 150 mg over 4 hours versus 14-mg teriflunomide oral tablets taken once daily. Identical in design, patients were randomized 1:1 to either agent and were assessed on ARR at 96 weeks as the primary end point.
Treatment with ublituximab, an investigational glycoengineered anti-CD20 monoclonal antibody, resulted in an ARR of 0.076 in ULTIMATE 1 compared to 0.188 for the teriflunomide-treated group, representing a relative reduction of 60% (ARR ratio, 0.406 [95% CI, 0.268-0.615]; P <.0001). Similarly, in ULTIMATE 2, ARRs at 96 weeks were 0.091 and 0.178 in the ublituximab and teriflunomide groups, respectively, equating to a 49% relative reduction (ARR ratio, 0.509 [95% CI, 0.330-0.784]; P = .0022).
The total number of T1 gadolinium (Gd)-enhancing lesions were reduced as a result of ublituximab treatment by 97% and 96% relative to treatment with teriflunomide in ULTIMATE 1 and 2, respectively (P <.0001). Additionally, relative reductions of 92% and 90% for new or enlarging T2 lesions were observed by treatment with ublituximab in ULTIMATE 1 and 2, respectively (P <.0001).
No evidence of disease activity (NEDA) status was observed in 44.6% of patients treated with ublituximab in ULTIMATE 1, representing a 198% improvement over teriflunomide (P <.0001). In ULTIMATE 2, 43% of ublituximab treated patients achieved NEDA representing at 277% improvement over teriflunomide (P <.0001). Additionally, at 12 weeks, 5.2% and 5.9% of ublituximab- and teriflunomide-treated patients, respectively, had confirmed disability progression (CDP), while only 3.3% of ublituximab-treated patients showed a 24-week CDP, compared to 4.8% of patients in the teriflunomide group. Neither was deemed statistically different.
A pre-specified pooled tertiary analysis looking at confirmed disability improvement (CDI) showed that 12% of those treated with ublituximab had 12-week CDI compared to 6% of those in the teriflunomide group, representing a 116% increased chance of improvement (P = .0003). Similarly, 9.6% and 5.1% of those in the respective groups had 24-week CDI, equating to a 103% increased chance (P = .0026).
Both treatment groups had similar number of adverse events (AEs), the most common being infusion-related reaction (IRR), headache, nasopharyngitis, and lymphopenia. No patients treated with teriflunomide had grade 4 severity of IRRs compared to 0.2% of those in the ublituximab group at weeks 1 and 3. IRRs were most frequent on the first dose, with 43% of those in the ublituximab group and 9.7% of those in the teriflunomide group reporting IRR on day 1. Most IRRs were mild to moderate and decreased in frequency with subsequent dosing.
Serious AEs (SAEs) occurred in 6.2% and 9.5% of the teriflunomide and ublituximab groups, respectively. The most common SAEs, occurring in at least 1% of any treatment group, was infections and infestations, as well as nervous system disorders.
Three deaths occurred in the trial, resulting from encephalitis, salpingitis, and pneumonia, all in the ublituximab group. Investigators deemed that the case of pneumonia was possibly related to treatment. Additionally, investigators saw no cases of progressive multifocal leukoencephalopathy.
Global study chair Lawrence Steinman, MD, Zimmerman Professor of Neurology and Neurological Sciences, and Pediatrics, Stanford University, sat down with NeurologyLive to provide insight into the use of ublituximab in MS and review results of the ULTIMATE 1 and 2 trials, which were originally presented at the American Academy of Neurology 2021 Annual Meeting. Watch what he had to say below.