Ofatumumab Maintains Efficacy in Patients on Previous Anti-CD20 Therapy

Le Hua, MD

Newly announced interim data from OLIKOS, a single-arm, prospective, phase 3b study (NCT04486716), showed that treatment with subcutaneous ofatumumab (Kesimpta; Novartis) maintained its efficacy in patients with relapsing multiple sclerosis (MS) who were previously treated with an anti-CD20 therapy of either ocrelizumab (Ocrevus; Genentech) or rituximab.¹

These data were presented as a late-breaker by Le Hua, MD, director of the Multiple Sclerosis Program at Cleveland Clinic’s Lou Ruvo Center for Brain Health at MSMilan 2023, the 9th Joint ECTRIMS-ACTRIMS Meeting, held October 11-13, in Milan, Italy. All told, 6-month interim findings showed that 20 mg of subcutaneous ofatumumab was efficacious following the switch, with 100% of patients who had available MRI assessment data meeting the primary efficacy end point of no change or reduction in the number of gadolinium-enhancing (Gd+) lesions.

The trial screened 145 patients aged 18 to 60 years with relapsing MS per the 2017 revised McDonald criteria who received at least at least 2 consecutive intravenous courses of anti-CD20 therapy, with the last dose being 4 to 9 months before the trial’s baseline. Spanning across 21 centers in the US, enrolled patients also had Expanded Disability Status Scale (EDSS) scores less than or equal to 5.5 and were neurologically stable for 1 month before receiving ofatumumab. Following screening failures, 102 patients were included in the full analysis set (FAS), with 18 of these having MRI assessments outside of the 6-month window and 7 with no MRI data at all.

Among those included, the trial was comprised of mainly females (67.6%), patients of White race (76.5%), and had a mean age of 43.5 years. Coming into the study, only 1 patient was previously on rituximab, while the rest (n = 101) had taken ocrelizumab. Of note, the trial mainly included relapsing-remitting MS (n = 100); however, there were 2 patients with secondary progressive MS at study entry. Throughout the trial, patients received ofatumumab 20 mg subcutaneously once monthly for 12 months following an initial loading regimen of 20-mg subcutaneous doses on days 1, 7, and 14.

READ MORE: B Cell Suppression Not Correlated With Therapeutic Response in Ocrelizumab-Treated Patients

For those with MRI assessments outside of the 6-month window (n = 18), no Gd+ type 1 lesions were identified following treatment with ofatumumab. At the 6-month mark, mean immunoglobulin and IgM level concentrations were within the normal reference ranges observed at baseline. Additionally, at this time point, mean CD19+ b-cell concentration decreased from 25.39 cells/uL at baseline to 0.54 cells/uL.

In terms of safety, treatment-emergent adverse events (TEAEs) were recorded in 75.5% of patients, with COVID-19 (14.7%), fatigue (9.8%), headache (8.8%), urinary tract infection (6.9%), pruritus (5.9%), and dizziness (4.9%) as the most common TEAEs. Only 1 patient experienced a serious TEAE and 1 patient discontinued because of TEAEs. The most common injection site and injection systemic reactions were injection site pain (3.9%) and headache (4.9%), respectively.

Initiated midway through 2021, OLIKOS is still ongoing with a planned completion after 12 months of treatment. The trial will continue to evaluate the primary end point of change or reduction in Gd+ lesions count at month 12, with secondary end points of participation retention, changes in immune biomarkers, treatment satisfaction, safety, and tolerability.

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REFERENCE
1. Hua LH, Brown B, Camacho E, et al. OLIKOS study: 6-month interim efficacy and safety in patients with relapsing multiple sclerosis who switched to subcutaneous ofatumumab from intravenous anti-CD20 therapies. Presented at: MSMilan; October 11-13; Milan, Italy. Poster 784