The novel B-cell therapy has been assigned a PDUFA date of June 2020.
Stephen Hauser, MD
The FDA has accepted the supplemental biologics license application for ofatumumab (Novartis), a novel B cell-targeting therapy indicated for the treatment of relapsing forms of multiple sclerosis (MS).1
The drug, a fully human antibody targeting CD20-positive B cells, was also simultaneously accepted for review by the European Medicines Agency.
The therapy, which is administered monthly via subcutaneous injection, demonstrated significant efficacy over teriflunomide (Aubagio; Sanofi Genzyme) in the head to head phase 3 ASCLEPIOS I and II trials, which included 1882 patients with MS age 18 to 55.
Treatment with 20 mg ofatumumab once monthly was associated with 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. It also significantly 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.2
"I think the stunning effect size [of ofatumumab] against the relapsing focal inflammation of MS is what was so remarkable here, in a drug that can be self administered by subcutaneous injection, rather than requiring an infusion," primary investigator Stephen Hauser, MD, director of the UCSF Weill Institute for Neurosciences, told NeurologyLive after presenting top-line data at ECTRIMS 2019. "This is also a fully human antibody that has a side effect profile that was difficult to distinguish from sham injections."
Novartis also recently completed the phase 2 APLIOS study which will report on bioequivalence between administration of ofatumumab via a pre-filled syringe, which was used in the ASCLEPIOS trials, and an autoinjector pen. Positive results from that trial will be presented at the upcoming ACTRIMS meeting in West Palm Beach, Florida.
“I think one advantage [of ofatumumab] is that patients and insurers are spared the cost of infusions, which can be extremely costly. Also, because ofatumumab is a fully human molecule—the only fully human CD20—it is potentially better tolerated over the long term,” Hauser told NeurologyLive.2 “The mode of administration is probably a formula that many patients will like; they can take the drug by themselves just once a month.”
The FDA has assigned a PDUFA date of June 2020 for ofatumumab.
1. 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.
2. Novartis ofatumumab demonstrates superiority versus Aubagio® in two head-to-head Phase III multiple sclerosis studies [press release]. Basel, Switzerland: Novartis; Published August 30, 2019. novartis.com/news/media-releases/novartis-ofatumumab-demonstrates-superiority-versus-aubagio-two-head-head-phase-iii-multiple-sclerosis-studies. Accessed February 24, 2020.