The investigational MS therapy is currently under review with the FDA, with a PDUFA date set for June 2020.
Amit Bar-Or, MD, FRCPC
Results of the open-label APLIOS study suggest that treatment with ofatumumab nearly completely depletes B cells over 12 weeks of treatment via an at-home autoinjector, which was found to be bioequivalent to a prefilled syringe of the multiple sclerosis treatment.
The results were presented at the 2020 America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 27-29, 2020, in West Palm Beach, Florida.
The supplemental biologics license application for the novel, fully human antibody targeting CD20-positive B cells, was recently accepted by the FDA, who assigned a PDUFA date sometime in June 2020. Notably, the filing was supported by data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab administered via a prefilled syringe to treatment with teriflunomide (Aubagio; Sanofi Genzyme).
In those trials, treatment with 20 mg ofatumumab once monthly resulted in over a 50% reduction in annualized relapse rate in ASCLEPIOS I and II (50.5% and 58.5%; P <.001 for both), respectively, compared with treatment with teriflunomide. The drug was also significantly associated with reduced inflammatory disease activity as demonstrated by the lack of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions. Secondary outcomes were also met, including a 34.4% (P = .002) and 32.5% (P = .012) relative risk reduction in 3- and 6-month confirmed disability progression compared with teriflunomide.
In an effort to ease treatment burden on patients and encourage self-administration of the drug at home, investigators launched the 12-week, open-label, phase 2BE APLIOS study, which included 284 patients who were randomly assigned to receive 20 mg subcutaneous ofatumumab once monthly administered via autoinjector (n = 128) or prefilled syringe (n = 130) to the abdomen or to the thigh (n = 13 for each). The participants received initial loading doses on days 1, 7, and 14, with monthly injections taking place from week 4 onwards. B cell depletion was measured 9 times over the 12-week study, with area under the curve and max plasma concentration use to determine pharmacokinetic bioequivalence.
At baseline, median B cell counts ranges from 210 to 220 cells/μL. The investigators reported that the loading doses were associated with a rapid depletion of B cells, dropping to a median of 2 to 4 cell/μL by day 14, with sustained levels of at ≤1 cell/μL by week 12. Low B cell counts were achieved as early as day 14 in the majority of patients (77%-87%), increasing to 92% to 95% by week 4. Notably, these low levels were maintained through week 12 in 97% to 100% of patients.
The investigators also found that the area under the curve and the maximum plasma concentration were similar between both administration groups who injected the abdomen (1.03 and 1.00).
“The results suggest that ofatumumab sc offers an effective B-cell depleting therapy using the patient-friendly AI SensoReady pen that allows for monthly at-home self-administration and can help reduce treatment burden,” they wrote.
For more coverage of ACTRIMS 2020, click here.
1. Bar-Or A., Fox E, Goodyear A, et al. Onset Of B-cell Depletion With Subcutaneous Administration Of Ofatumumab In Relapsing Multiple Sclerosis: Results From The APLIOS Bioequivalence Study. Presented at: 2020 ACTRIMS Forum. Abstract LB300.
2. Novartis announces FDA and EMA filing acceptance of ofatumumab, a novel B-cell therapy for patients with relapsing forms of multiple sclerosis (RMS) [news release]. Basel, Switzerland: Novartis. February 24, 2020. globenewswire.com/news-release/2020/02/24/1988939/0/en/Novartis-announces-FDA-and-EMA-filing-acceptance-of-ofatumumab-a-novel-B-cell-therapy-for-patients-with-relapsing-forms-of-multiple-sclerosis-RMS.html. Accessed February 24, 2020.