Novartis‘s ofatumumab outperformed Aubagio (teriflunomide) at lowering the frequency of relapses and preventing disability progression among people with relapsing forms of multiple sclerosis (MS), a study based on clinical trial data reports.
The study, “Ofatumumab versus Teriflunomide in Multiple Sclerosis,” was published in The New England Journal Of Medicine.
Ofatumumab is an antibody therapy that works by targeting CD20, a protein found on the surface of B-cells, a type of immune cell. By binding to CD20, ofatumumab is thought to lead to the destruction of B-cells, which is thought to reduce inflammation in the central nervous system (the brain and spinal cord).
In the U.S., ofatumumab is approved to treat certain blood cancers under the brand name Arzerra. The medication is currently being reviewed by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a possible treatment for relapsing forms of MS.
Decisions are expected in September from the FDA and early next year from the EMA.
This study reports the results of two Phase 3 clinical trials — ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231) — which directly compared ofatumumab (20 mg subcutaneous injections once a month) to Aubagio (14 mg oral tablets taken once daily).
Collectively, the trials enrolled 1,882 people with relapsing MS, which includes relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS). They were conducted at 385 sites in 37 countries; 946 patients were treated with ofatumumab, and 936 with Aubagio.
Of note, ofatumumab is designed to be a self-administered subcutaneous (under-the-skin) injection using an autoinjector pen, rather than being given via infusion in a hospital setting. If approved, it will be the first B-cell therapy that can used at the home.
Patients in both trials were followed for up to 2.5 years (median time in trial, 1.6 years). After the first four injections, most (74.4%) of those being given ofatumumab administered their own treatment at home.
The trials’ primary endpoint, its main measure of efficacy, was changes in annual relapse rates. This rate was significantly lower among patients treated with ofatumumab relative to those given Aubagio — 0.11 vs. 0.22 relapses each year in ASCLEPIOS I, and 0.10 vs. 0.25 in ASCLEPIOS II.
These findings amounted to ofatumumab reducing patients’ annual relapse rates by 51% in ASCLEPIOS I and by 58% in ASCLEPIOS II compared with Aubagio.
In a pooled analysis from both trials, significantly fewer patients treated with ofatumumab experienced confirmed disability progression after three months (10.9% vs. 15% in the Aubagio group) or six months (8.1% vs. 12%). The relative risk of disability reduction at these two time points was 34% and 32%, respectively.
More trial participants using ofatumumab experienced a lessening in disability after six months; however, this difference did not reach statistical significance.
Ofatumumab treatment also significantly decreased MRI lesions — both T1 lesions (which indicate areas of ongoing inflammation) and T2 lesions (which indicate areas of damage to brain structures, regardless of inflammatory status). In ASCLEPIOS I, the average number of T1 lesions was reduced by 97%, and that of T2 lesions by 82%. Similar results were seen in ASCLEPIOS II: 94% for T1 and 85% for T2 lesions.
Compared with Aubagio, treatment with ofatumumab significantly lowered the levels of neurofilament light chain — a marker of damage in the nervous system — at multiple time points.
“The ASCLEPIOS studies found that ofatumumab produced a significant reduction in new inflammation, as well as fewer clinical relapses and progression events,” Stephen L. Hauser, MD, a study co-author and director of the UCSF Weill Institute for Neurosciences, said in a Novartis press release.
The safety profile of both medications was comparable. Similar numbers of people in the two treatment groups experienced any adverse events (83.6% with ofatumumab and 84.2% with Aubagio), rates of infections (51.6% and 52.7% with Aubagio), and cancers (0.5% and 0.4% with Aubagio).
The most common side effects associated with ofatumumab, which occurred in at least 10% of treated patients, were injection-related reactions, nasopharyngitis (the common cold), headache, injection-site reactions, upper respiratory tract infections, and urinary tract infections.
“Ofatumumab represents a potential new option for [relapsing] MS patients with greater efficacy compared to teriflunomide, a comparable safety profile, and the convenience of once monthly self-administration without the need for infusions,” Hauser said.
Krishnan Ramanathan, neuroscience global program head at Novartis, added: “ASCLEPIOS I and II demonstrate the efficacy and safety of ofatumumab and its potential to become a first-choice treatment option that offers [relapsing] MS patients the flexibility as they continue to live their lives.”
If approved, ofatumumab will be the first B-cell therapy that can be self-administered at home.
“The results of these trials do not permit any inferences to be made about the efficacy of ofatumumab as compared with other drugs for multiple sclerosis that are considered to be more potent than teriflunomide,” the researchers wrote.
They also recommended larger and longer trials “to determine the long-term effect and risks of ofatumumab as compared with other disease-modifying treatments, including other anti-CD20 monoclonal antibodies.”
Three of this study’s 23 researchers are Novartis employees and the company financially supported this work.