The first (MS) received FDA approval on Thursday, Novartis announced.
Ofatumumab (Kesimpta), an antibody targeting CD20-positive B cells, is approved for adult patients with clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, the company said.
"This approval is wonderful news for patients with relapsing multiple sclerosis," Stephen Hauser, MD, of the University of California San Francisco, who led ofatumumab clinical trials, said in a statement from the drugmaker. "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."
Like ocrelizumab (Ocrevus), which was approved in 2017 for relapsing and primary progressive MS, and (Rituxan), which is used off-label in MS, ofatumumab binds to CD20 molecules, resulting in B-cell depletion. In 2009, ofatumumab was approved to treat chronic lymphocytic leukemia under the brand name Arzerra.
Ofatumumab's approval in MS was based on results of two phase III trials, and . In these studies, 20-mg monthly subcutaneous injections of ofatumumab bested daily 14-mg teriflunomide (Aubagio) oral tablets in reducing annualized relapse rates (ARR), 3-month confirmed disability progression, and the number of gadolinium-enhancing T1 and new or enlarging T2 lesions in relapsing MS.
In ASCLEPIOS I, monthly injections of ofatumumab showed a 50.5% relative reduction in ARR compared with oral teriflunomide; in ASCLEPIOS II, the ARR of ofatumumab bested that of teriflunomide by 58.5%.
"The absolute numbers of relapses -- the annualized relapse rate of about one [relapse] in 10 years -- may come close to the floor that we're going to be able to see in a population of this type," Hauser said when he presented trial results at the 2019 ECTRIMS Congress. "There were low relapse rates in teriflunomide, but very, very low relapse rates in the ofatumumab group."
A separate post-hoc analysis showed ofatumumab may halt new disease activity in relapsing MS patients. The proportion of patients achieving no evidence of disease activity (NEDA-3; no relapses, no MRI lesions, and no disability worsening combined) with ofatumumab versus teriflunomide was significantly higher at months 0 to 12 (47.0% vs 24.5%, P<0.001) and at months 12 to 24 (87.8% vs 48.2%, P<0.001), Novartis said.
From the patient standpoint, self-injected ofatumumab may be more appealing than IV infusion treatments like ocrelizumab, Mar Tintoré, MD, PhD, of University Hospital Vall d'Hebron in Barcelona, said at ECTRIMS.
"The advantage for the patient can be significant; you can give the treatment yourself," said Tintoré, who was not part of the ASCLEPIOS trials. But the downside with ofatumumab is that clinicians are less sure about the drug's administration, she pointed out. "We're a little bit afraid to not control the treatment," she said. "With IVs, we know the patient has received the treatment. We're more aware of what happened."
Ofatumumab had a favorable safety profile with no unexpected safety signals, Hauser said. Its safety profile was comparable to teriflunomide's, with the frequency of serious infections and malignancies similar across both treatment groups, Novartis reported. Upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions were the most commonly observed adverse reactions (incidence greater than 10%).
Hepatitis B virus and quantitative serum immunoglobulins screening are required before the first ofatumumab dose. The dosing schedule calls for 20 mg administered at weeks 0, 1, and 2, with 20 mg administered monthly starting at week 4.
Ofatumumab should be with active infections. Immunoglobulins at the beginning, during, and after stopping treatment should be monitored until B-cell repletion. Consider discontinuing the drug if a patient develops a serious opportunistic infection or recurrent infections, or if immunoglobulin levels indicate immune compromise, Novartis said.