IV Ofatumumab Reduces Relapses in MS, But Not Better Than Kesimpta
63% into-the-vein reduction rate lower than approved under-the-skin therapy
An intravenous (into-the-vein) formulation of ofatumumab — a disease-modifying therapy for multiple sclerosis (MS) sold under the brand name Kesimpta — resulted in a 63% reduction in relapse rates among MS patients, with about 60% remaining relapse-free over the first year of treatment, a recent study in Denmark found.
However, relapse reduction with this formulation was inferior to that seen with the approved formulation of Kesimpta, which is administered subcutaneously, or under the skin.
Moreover, more patients on into-the-vein ofatumumab experienced infusion-related reactions compared with those on other intravenous CD20 antibodies often used in MS, the researchers noted.
Notably, however, this formulation of ofatumumab was used for these individuals as an off-label treatment option, meaning “the results reflect a patient population for whom the treating neurologists had deemed approved treatment options exhausted,” the team wrote.
While that “reduces [the] generalizability” of the findings, the researchers nonetheless concluded that this formulation “reduces relapse rate and stabilizes disability worsening with an acceptable safety profile.”
MS is a neurodegenerative disease in which the immune system erroneously mounts an attack that damages the myelin sheath, a protective cover around nerve fibers that’s important for neuronal communication.
B-cells, the immune cells responsible for making antibodies, are a key player in the development and progression of this condition, and also play a major role in other demyelinating diseases like neuromyelitis optica spectrum disease (NMOSD) and myelin-oligodendrocyte glycoprotein associated disease (MOGAD).
Thus, CD20 antibodies that aim to eliminate B-cells and reduce antibody production are increasingly being used in these conditions to dampen the inflammatory attack.
Kesimpta as an MS treatment
Its approval was based on data from the ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231) Phase 3 clinical trials, which compared Kesimpta against the approved oral MS treatment Aubagio (teriflunomide). The trials involved 1,882 MS patients.
In these trials, and as compared with Aubagio, Kesimpta significantly lowered relapse rates, reduced the risk of disability worsening, and prevented the development of new or enlarging lesions.
Notably, the active ingredient in Kesimpta, ofatumumab, was first approved under the brand name Arzerra as an intravenous treatment for chronic lymphocytic leukemia, a B-cell cancer. Until 2019, when Arzerra was discontinued in Europe, some patients with MS, NMOSD, and MOGAD were treated off-label with this intravenous formulation at the Danish Multiple Sclerosis Center.
Now, researchers at this center set out to investigate the safety and efficacy of intravenous ofatumumab in these patients. The team retrospectively analyzed data from 50 patients who received the medicine from February 2013 to April 2019, for a median duration of 2.2 years.
Of those, the majority (70%) had MS. Specifically, 35 had been diagnosed with RRMS and seven with progressive MS, while four had NMOSD, and another four had MOGAD.
The patients had a median age of 46, and more than 80% were women. Their median Expanded Disability Status Scale (EDSS) score was 4, meaning significant disability but no walking impairment.
The treatment consisted of two induction infusions — 300 mg followed by 1,000 or 300 mg — two weeks apart, followed by a maintenance infusion every six months of 1,000 or 600 mg.
After completing one year of treatment with intravenous ofatumumab, the rates of relapse in people with MS dropped by 63%. The relapse rates were 1.10 per year before ofatumumab to 0.41 per year after treatment. Similar reductions were observed in NMOSD and MOGAD.
“This was a smaller reduction than that observed in the ASCLEPIOS I and II phase III trials of [subcutaneous] ofatumumab, where [the annualized relapse rate] was reduced from 1.2 to 0.11 and 1.3 to 0.10, respectively,” the team wrote.
The number of patients across all diseases who remained relapse-free also increased, from 38% in the year before treatment to 60% in the first year of treatment, and to 63% in the second year of ofatumumab.
Also, 18% of patients experienced a confirmed disability progression (disease worsening), while about 6% experienced a confirmed disability improvement, or less disability. Among MS patients, the probability of having had a relapse after two years was 54% and the probability of confirmed disability progression was 8%, “which is in line with the ASCLEPIOS results (8.2% and 8.0%),” the researchers wrote.
The treatment had an acceptable safety profile, although a significant proportion of patients experienced infusion-related reactions — 86% on the first infusion and 42% on the last infusion).
“This is … somewhat higher than the frequencies reported for [Ocrevus] (∼28%-35%) and [rituximab] (42%-78.3%),” two other intravenous CD20 antibodies that are commonly used as a treatment for MS, the researchers noted. However, they said that was likely related to the slightly different mechanism of action of these antibodies.
In terms of severe reactions, 13% of patient were hospitalized at least once due to infections, with a median stay of four days. All cases of infection resolved with treatment.
Taken together, the results showed a “statistically significant change in relapse-free proportion of patients” given the intravenous medication.