Novartis’ anti-CD20 monoclonal antibody ofatumumab (Kesimpta) is administered once monthly at home, and is expected to be available for those with multiple sclerosis as early as September 2020.
Stephen L. Hauser, MD, director, UCSF Weill Institute for Neurosciences, and professor of neurology, UCSF School of Medicine
Stephen L. Hauser, MD
Novartis has announced that the FDA has granted market approval to ofatumumab (Kesimpta) for the treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome (CIS), relapsing-remitting disease, and active secondary progressive MS.1
The subcutaneous injection therapy is a precision targeted B-cell agent administered once monthly at home via the Sensoready autoinjector pen. Novartis noted that it anticipates the therapy to become available in the US as early as September, with additional regulatory submissions ongoing and expected approval in Europe by the first half of 2021.
This decision followed a June announcement by Novartis that the FDA had delayed its regulatory decision on ofatumumab. The fully human anti-CD20 monoclonal antibody is already approved in the US and Europe as first-line treatment for chronic lymphocytic leukemia (CLL) and recurring CLL. In that indication, it is marketed under the name Arzerra.
“This approval is wonderful news for patients with relapsing multiple sclerosis. In the key clinical studies, this breakthrough treatment produced a profound reduction in new brain lesions, reducing relapses and slowing underlying disease progression,” said Stephen L. Hauser, MD, director, UCSF Weill Institute for Neurosciences, and co-chair, steering committee for the ASCLEPIOS I and II studies, in a statement. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center.”
Novartis’ supplemental biologics license application was supported by data from the phase 3 ASCLEPIOS I and II trials (NCT02792218 and NCT02792231), which featured more than 1800 patients and pitted the agent against teriflunomide (Aubagio; Sanofi Genzyme), an oral inhibitor of pyrimidine synthesis that reduces T-cell and B-cell activation. Overall, the trial randomly assigned 946 patients to receive ofatumumab and 936 to receive teriflunomide.
Earlier this month, the full results of the trials were published, showing that annualized relapse rates (ARR) for patients with MS were reduced by 51% (ofatumumab: 0.11; teriflunomide: 0.22; difference, −0.11; 95% CI, −0.16 to −0.06; P <.001) and 58% (ofatumumab: 0.10; teriflunomide: 0.25; difference, −0.15; 95% CI, −0.20 to −0.09; P <.001) in those who received ofatumumab in the ACLEPIOS I and II trials, respectively, with both differences achieving statistical significance (P <.001 for both).2
There was also a significant reduction in gadolinium-enhancing (Gd+) T1 lesions observed, with a 97% and 94% relative reduction in ASCLEPIOS I and II, respectively (P <.001 for both). Additionally, there was an 82% and 85% relative reduction in new or enlarging T2 lesions in ASCLEPIOS I and II, respectively (P <.001 for both).
In a pre-specified meta-analysis, the risk of 3-month and 6-month confirmed disability worsening (CDW) were reduced by 34% (P = .002) and 32% (P = .01), respectively, with ofatumumab. In the pooled data, the percentage of patients with 3-month CDW was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio [HR], 0.66; P = .002), and at 6 months was 8.1% and 12.0%, respectively (HR, 0.68; P = .01). At 6 months, the percentage of patients with confirmed disability improvement was 11.0% and 8.1% (HR, 1.35; P = .09), respectively.
“Multiple sclerosis (MS) is a complex disease, and response to disease modifying treatment will vary among individuals,” said Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society, in a statement.1 “This makes it important to have a range of treatments available with different mechanisms of action and routes of administration. We are pleased to have an additional option approved for the treatment of relapsing forms of MS.”
Secondary end point findings from the ASCLEPIOS data showed superiority of ofatumumab in the reduction of neuroaxonal damage, with the group showing a 7% lower concentration of neurofilament light chain at 3 months (P = .01), 27% lower at 12 months, and 23% lower at 24 months in ASCLEPIOS I. The corresponding differences in ASCLEPIOS II were 11% (P <.001), 26%, and 24%, respectively.
The safety profile demonstrated was similar to teriflunomide, with the frequency of serious infections and neoplasms being comparable between the treatment groups. Injection-related reactions occurred in 20.2% of the ofatumumab group and in 15.0% of the teriflunomide group. Nasopharyngitis, headache, injection-site reaction, upper respiratory tract infection, and urinary tract infection were the most commonly observed adverse events (AEs) with ofatumumab, occurring in ≥10% of patients. Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.
Recently, in a virtual NeurologyLive Peers and Perspectives segment, Matthew J. Baker, MD, and Jeffrey M. Kaplan, MD, shared their thoughts on results from the APLIOS bioequivalence study and treatment of appropriate patients with ofatumumab for relapsing multiple sclerosis. Watch the video below.
1. FDA approves Novartis Kesimpta® (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. News release. Novartis. August 20, 2020. Accessed August 20, 2020. https://www.globenewswire.com/news-release/2020/08/20/2081597/0/en/FDA-approves-Novartis-Kesimpta-ofatumumab-the-first-and-only-self-administered-targeted-B-cell-therapy-for-patients-with-relapsing-multiple-sclerosis.html
2. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020;383:546—557. doi: 10.1056/NEJMoa1917246