Omalizumab Biosimilar Shows Equivalent Efficacy as Multiple Sclerosis Treatment

The biosimilar ocrelizumab candidate (Xacrel) was found to be equivalent to the originator product (Ocrevus) in reducing the annualized relapse rate and showed comparable safety and efficacy over 96 weeks in patients with relapsing multiple sclerosis (RMS), as confirmed in a randomized trial.¹

The randomized, 2-armed, double-blind, phase 3 study from Iran (NCT04966338), published in Scientific Reports, was conducted to assess the equivalency of the biosimilar ocrelizumab candidate to the originator product in reducing the annualized relapse rate (ARR) in patients with RMS, highlighting the importance of increasing patient access to effective, cost-efficient treatments for a disease that significantly impacts global health.

MS is an autoimmune disease affecting around 3 million people globally, characterized by immune cells attacking the central nervous system's myelin, leading to disability.² MS can cause cognitive impairment, fatigue, and various other symptoms. It is classified into relapsing-remitting, secondary progressive, and primary progressive forms. High-efficacy disease-modifying therapies (DMTs) are used to manage MS, with B cell-targeting treatments like ocrelizumab showing effective results in reducing relapse rates. Biosimilars offer a way to increase access to MS treatments, especially in lower-income areas.

The study was conducted between August 2019 and October 2021 across 15 centers in Iran. It involved adult patients with RMS who met specific inclusion criteria. Participants were randomly assigned (1:1) to receive either 300 mg of Xacrel or Ocrevus for the first 2 doses (administered every 2 weeks), followed by 600 mg every 24 weeks for 96 weeks.

Prior to each infusion, patients received 100 mg intravenous methylprednisolone, an antihistamine (chlorpheniramine), and an antipyretic (acetaminophen) to minimize infusion reactions.

The primary goal was to evaluate the equivalency of Xacrel to Ocrevus in reducing the ARR at week 48. Secondary outcomes included disability progression, relapse-free patients at 96 weeks, and MRI changes in brain lesions. Safety was assessed through the incidence of adverse events (AEs) and infusion reactions.

Randomization was stratified by baseline disability status (EDSS), and participants were blinded to the treatment arm. Statistical analyses included Poisson regression, Cox regression, and Kaplan-Meier methods for the primary and secondary outcomes, ensuring equivalency between the 2 treatments.

A total of 170 patients were enrolled (85 per treatment group), with a 10% dropout rate accounted for. Patients had to be 18 to 55 years of age and have a history of at least 2 documented relapses in the last 2 years or 1 documented relapse in the last year before the screening visit.

The primary efficacy measure, the ARR at 48 weeks, showed similar results between the 2 groups. In the per-protocol (PP) set, the ARR for Xacrel was 0.067 (95% CI, 0.029-0.155), and for Ocrevus, it was 0.070 (95% CI, 0.031-0.158), with no significant difference (95% CI, −0.080 to 0.075; P = .95). The results were consistent in the intent-to-treat (ITT) set, where the ARR was 0.065 for Xacrel (95% CI, 0.028-0.149) and 0.068 for Ocrevus (95% CI, 0.030-0.153), again showing no significant difference (95% CI, −0.078 to 0.072; P = .95).

Over the 96-week period, the confirmed disability progression rate at 12 weeks was 7.06% for Xacrel and 5.90% for Ocrevus (P = .71), and at 24 weeks, it was 7.06% for Xacrel and 2.35% for Ocrevus (P = .16). Regarding relapse-free rates at 96 weeks, 89.41% of patients in the Xacrel group and 87.10% in the Ocrevus group remained relapse-free (P = .63). In MRI assessments, the mean number of new or enlarging T2 hyperintense lesions was 0.16 for Xacrel (95% CI, 0.08-0.33) and 0.08 for Ocrevus (95% CI, 0.03-0.20), with no significant difference (P = .21). The volume of T2 lesions decreased similarly in both groups (Xacrel, −0.60; Ocrevus, −0.70; P =.88).

Regarding safety, 97.65% of patients in both groups experienced at least 1 adverse event (AE), with infusion-related reactions being the most common. In total, 24 serious AEs (SAEs) were reported, with 6 in the Xacrel group and 15 in the Ocrevus group. There was no significant difference in the incidence of SAEs between the 2 groups. Serious infections occurred in both groups, including cases of coronavirus, pharyngitis, urinary tract infection, and appendicitis.

No positive samples for anti-ocrelizumab antibodies were found in the immunogenicity assessment, indicating no immunogenic response to Ocrevus. A post hoc analysis of ARR at 96 weeks revealed no significant difference (Xacrel, 0.122; Ocrevus, 0.124; P = .82), and the proportion of patients with CD19 levels below 1% at least once was similar between the 2 groups (Xacrel, 64.71%; Ocrevus, 63.53%; P = .87).

The study had limitations. The COVID-19 pandemic affected patient adherence and attendance at scheduled visits, potentially influencing results. Variability in MRI instruments between study centers could also have introduced inconsistencies in the MRI data. Despite these limitations, the results suggest that Xacrel is a viable alternative to Ocrevus in treating RMS.

References

1. Sahraian MA, Abolfazli R, Shaygannejad V, et al. Evaluating efficacy and safety of ocrelizumab biosimilar (Xacrel) compared to the originator (Ocrevus) in relapsing multiple sclerosis: a phase III, randomized, equivalency, clinical trial. Sci Rep. 2024;14(1):24921. doi:10.1038/s41598-024-75745-y

2. Global Regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the global burden of Disease Study 2021. Lancet Neurol. 2024;23(4):344-381. doi:10.1016/s1474-4422(24)00038-3