With ofatumumab (Arzerra, Novartis), a fully human anti-CD20 monoclonal antibody, there is a greater likelihood of there being no evidence of disease activity (NEDA-3) for patients with relapsing multiple sclerosis (MS) compared to the disease-modifying therapy (DMT) teriflunomide, a new study shows.
The drug, which is already approved for the treatment of chronic lymphocytic leukemia, is currently under review for relapsing MS as a once-per-month self-injected therapy that could offer a convenient alternative to DMTs that require in-office infusion.
The new findings are from a pooled analysis from the phase 3 ASCLEPIOS I/II trials of the use of ofatumumab for patients with relapsing MS. There were 927 patients in the ASCLEPIOS I trial and 955 in the ASCLEPIOS II trial. The trials were conducted in 37 countries and involved patients aged 18 to 55 years.
The late-breaking research was presented as part of 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
The studies compared patients who were treated with subcutaneous ofatumumab 20 mg to patients treated with oral teriflunomide 14 mg once daily for up to 30 months. The average duration of follow-up was 18 months.
NEDA-3, commonly used to determine treatment outcomes for patients with relapsing MS, was defined as a composite of having no worsening of disability over a 6-month period (6mCDW), no confirmed MS relapse, no new/enlarging T2 lesions, and no gadolinium-enhancing T1 lesions.
The pooled results showed that the odds of achieving NEDA-3 during the first 12 months were three times greater with ofatumumab than with teriflunomide (47.0% vs 24.5%; odds ratio [OR], 3.36; P < .001) and were more than eight times greater from months 12 to 24 (87.8% vs 48.2%; OR, 8.09; P < .001).
In addition, compared to patients who received teriflunomide, a higher proportion of patients who received ofatumumab were free from 6mCDW over 2 years (91.9% vs 88.9%), as well as from relapses (82.3% vs 69.2%) and lesion activity (54.1% vs 27.5%).
There was a significantly greater reduction in annualized relapse rate with ofatumumab compared with teriflunomide at all cumulative time intervals, including months 0 to 3 (P = .011), and at all subsequent time intervals from month 0 to 27 (P < .001).
The pooled findings further showed that ofatumumab reduced the mean number of gadolinium-enhancing T1 lesions per scan by 95.9% compared to teriflunomide (P < .001).
“Ofatumumab increased the probability of achieving NEDA-3 and demonstrated superior efficacy vs teriflunomide in patients with relapsing MS,” said the authors, led by Stephen L. Hauser, MD, of the Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, California.
Ofatumumab Superior in Primary, Secondary Outcomes
As previously reported by Medscape Medical News, subcutaneous ofatumumab also demonstrated superior efficacy over oral teriflunomide in the primary and secondary endpoints in the ASCLEPIOS I/II trials. The annualized relapse rate was reduced by 0.22 in the teriflunomide group, vs 0.11 in the ofatumumab group (50.5% relative reduction; P < .001) in the ASCLEPIOS I trial, and by 0.25 vs 0.10 (58.5% relative reduction P < .001) in ASCLEPIOS II.
Ofatumumab also reduced the number of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions compared to teriflunomide (all P < .001). It reduced the risk for disability progression by 34.4% over 3 months and by 32.5% over 6 months.
In the studies, the rate of serious infection with ofatumumab was 2.5%, compared to 1.8% with teriflunomide. Rates of malignancies were 0.5% and 0.3%, respectively.
“Ofatumumab demonstrated superior efficacy vs teriflunomide, with an acceptable safety profile, in patients with relapsing MS,” the authors reported.
Adherence Rates With Self-Injection Encouraging
An additional analysis from the two trials presented virtually in a separate abstract at the CMSC shows greater adherence to the self-administered regimen.
The analysis shows that in the ASCLEPIOS I study, 86.0% patients who were randomly assigned to receive ofatumumab and 77.7% who received teriflunomide completed the study on the assigned study drug. The proportion of patients who received ofatumumab and who discontinued treatment was 14.0%, vs 21.2% for those in the teriflunomide group.
The most common reasons for discontinuation were patient/guardian decision (ofatumumab, 4.9%; teriflunomide, 8.2%), adverse event (ofatumumab, 5.2%; teriflunomide, 5.0%), and physician decision (ofatumumab, 2.2%; teriflunomide, 6.5%).
In the ASCLEPIOS II study, the rates were similar in all measures.
“In ASCLEPIOS trials, compliance with home-administered subcutaneous ofatumumab was high, and fewer patients discontinued ofatumumab as compared to teriflunomide,” the authors conclude.
Ofatumumab is currently under review by the US Food and Drug Administration for the treatment of relapsing forms of MS in adults. A decision on the approval is expected in June.
Comparator Drug a Weak Choice?
In commenting on the research, Stephen Kamin, MD, professor, vice chair, and chief of service, Department of Neurology, Rutgers New Jersey Medical School, in Newark, New Jersey, noted that a limitation of the ASCLEPIOS trials is the comparison with teriflunomide.
“The comparator drug, teriflunomide, is one of the least effective DMAs, and one that some clinicians, including myself, don’t use,” he said.
Previously, when asked by Medscape Medical News about the choice of teriflunomide as the comparator, Hauser noted that considerable discussion had gone into the decision.
“The rationale was that we wanted to have a comparator that would be present not only against focal disease activity but also potentially against progression, and we were also able to blind the study successfully,” he said at the time.
Kamin commented that ofatumumab will nevertheless likely represent a welcome addition to the tool kit of treatment options for MS.
“Any new drug is helpful in adding to our choices as a general rule,” he said. “Subcutaneous injection does have increased convenience.”
It is not likely that the drug will be a game changer, he added, although the treatment’s efficacy compared to other drugs remains to be seen.
“There has been another subcutaneous monoclonal for MS, daclizumab, although this was withdrawn from the market due to severe adverse effects not related to route of administration,” he added.
Hauser has relationships with Alector, Annexon, Bionure, Molecular Stethoscope, Symbiotix, and F. Hoffmann-La Roche. Kamin has received research support from Biogen, Novartis and CMSC.
Consortium of Multiple Sclerosis Centers (CMSC) 2020 Annual Meeting.