STOCKHOLM – (MS), according to research presented at the annual congress of the European Committee for Treatment and Research in MS. Ofatumumab also reduces the risk of 3-month and 6-month confirmed disability worsening, compared with teriflunomide. The former therapy has a favorable safety profile, and the investigators did not observe any unexpected safety findings.
Ofatumumab is a fully human anti-CD20 monoclonal antibody that Novartis is developing as a monthly 20-mg subcutaneous infusion. “Targeting CD20-bearing B-cells has been shown to be an effective therapeutic against MS,” said
Two concurrent phase 3 trials
Dr. Hauser and colleagues conducted two contemporaneous phase 3 trials, ASCLEPIOS I and ASCLEPIOS II, to compare the efficacy and safety of ofatumumab with those of teriflunomide. The two multicenter trials were double blinded and had a parallel-group design. Eligible patients were between ages 18 and 55 years; had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5; and had had one or more relapse in the previous year, two or more relapses in the previous 2 years, or a positive gadolinium-enhancing MRI scan during the year before randomization. Patients with progressive MS, neuromyelitis optica, or progressive multifocal leukoencephalopathy were excluded.
The investigators randomized patients in equal groups to receive 20-mg subcutaneous injections of ofatumumab every 4 weeks (plus a daily oral placebo) or 14 mg/day of teriflunomide orally (plus placebo subcutaneous injections). Participants randomized to ofatumumab underwent an initial loading regimen of 20-mg subcutaneous doses on days 1, 7, and 14. The trials had flexible durations: The number of events determined the length of the studies, which could last for as long as 30 months. At study completion, participants were enrolled into an ongoing, open-label extension study.
The primary endpoint of both trials was the annualized relapse rate (ARR). Among the secondary endpoints were 3- and 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI-related outcomes, and serum neurofilament light chain (NfL) levels.
Ofatumumab improved clinical and imaging outcomes
In all, 927 patients were randomized in ASCLEPIOS I (462 to teriflunomide and 465 to ofatumumab), and 955 patients were randomized in ASCLEPIOS II (474 to teriflunomide and 481 to ofatumumab). The study completion rate was approximately 85% in ASCLEPIOS I and approximately 82% in ASCLEPIOS II. The two studies had similar populations, and the two treatment arms in each trial were well balanced. Overall, mean age was approximately 38 years, 68% of patients were female, mean disease duration was approximately 8 years, and mean EDSS score was about 3.
Compared with teriflunomide, ofatumumab reduced the ARR by 50.5% in ASCLEPIOS I and by 58.5% in ASCLEPIOS II. Ofatumumab reduced the risk of 3-month confirmed disability worsening by 34.4%, compared with teriflunomide, and reduced the risk of 6-month confirmed disability worsening by 32.5%, compared with teriflunomide. All of these differences were statistically significant. Ofatumumab tended to increase the likelihood of confirmed disability improvement, compared with teriflunomide, but the result was not statistically significant.
Ofatumumab was superior to teriflunomide on imaging and laboratory measures, as well. Compared with teriflunomide, ofatumumab significantly reduced gadolinium-enhancing T1 lesions by 97.5% in ASCLEPIOS I and by 93.8% in ASCLEPIOS II. In addition, ofatumumab significantly reduced new or enlarging T2 lesions by 82.0% in ASCLEPIOS I and by 84.5% in ASCLEPIOS II. At month 24, ofatumumab reduced serum NfL levels by 23% in ASCLEPIOS I and by 24% in ASCLEPIOS II, compared with teriflunomide.
In both studies, adverse events and serious adverse events were well balanced between treatment groups. The ofatumumab groups had a slight increase in injection-related reactions, compared with the teriflunomide groups. Most systemic injection reactions were mild to moderate.
Novartis Pharma funded the research. Dr. Hauser has received travel reimbursement from F. Hoffmann-La Roche and Novartis for meetings and presentations related to anti-CD20 therapies.