News from the ocrelizumab front

AAN 2019

News from the ocrelizumab front

3300 2200 Carlotta Foletti, PhD

In our ongoing coverage of the AAN Annual Meeting in Philadelphia, we are focusing on select posters reporting on studies of ocrelizumab, an intravenous humanised monoclonal antibody that selectively targets CD20-expressing B cells. Ocrelizumab has been approved for treatment of relapsing forms of multiple sclerosis (MS) and primary progressive MS (PPMS).1,2

CHORDS is a prospective, multicentre, open-label, Phase IIIb study that evaluates the effectiveness and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis (RRMS) who responded sub-optimally to prior disease-modifying therapy (DMT).3 In a poster by Vollmer and colleagues, the investigators reported on safety findings – including the frequency and severity of injection-related reactions (IRRs) – observed with ocrelizumab in the shorter-infusion time extension substudy of CHORDS.4 There are potential benefits to administering ocrelizumab over a shorter infusion time in terms of convenience and adherence from both the patients’ and healthcare practices’ perspectives. The CHORDS substudy showed that the majority of patients completed the shorter infusion within 2.5 hours. Grade 1 or 2 IRRs – none of them serious – were reported in 12.4% of patients. No IRRs of Grade 3 or 4 were observed. In conclusion, the CHORDS substudy showed that the shorter infusion regimen applied to patients with RRMS were not putting them at a greater risk for serious or life-threatening IRRs.

In OPERA I and II, two identical Phase III randomised, double-blind, double‑dummy trials in relapsing multiple sclerosis (RMS), ocrelizumab had previously shown superiority in preventing disability progression compared with interferon (IFN) β-1a. At AAN 2019, Hauser and colleagues presented a study to assess the efficacy of earlier initiation of, or switching to, ocrelizumab therapy on 48-week confirmed disability progression (CDP) in the open-label extension (OLE) of the pooled OPERA I and OPERA II trials.5 Of the patients who entered this OLE, 88.6% completed the 3-year follow-up in which they received sustained clinical benefits from ocrelizumab therapy. After 5 years of follow-up, the 48-week CDP benefits accrued in patients who had already received ocrelizumab in the double-blind phases of the OPERA trials were maintained compared with patients who had been randomised to IFN β-1a and switched to ocrelizumab at the start of the OLE. In conclusion, the OLE of the pooled OPERA trials confirms previous findings of sustained clinical benefits of ocrelizumab on disability progression in patients with RMS.

Ocrelizumab had previously demonstrated efficacy in reducing upper limb disability in the placebo-controlled Phase III ORATORIO study in ambulatory patients with PPMS.6 Patients in real-world clinical settings, however, are typically more disabled and non-ambulatory. To inform the design of ORATORIO-HAND, a Phase IIIb study in such patients, Giovannoni and colleagues conducted a subgroup analysis of the more disabled and older patients in ORATORIO.7 Based on the findings of this analysis, the investigators determined that ORATORIO-HAND would further investigate the efficacy of ocrelizumab on upper limb function in a PPMS population aged 18–65 years with an Expanded Disability Status Scale (EDSS) score of 3.0–8.0 and a 9-Hole Peg Test (9HPT) completion time at baseline greater than 25 s. Screening for ORATORIO-HAND will begin in the second quarter of 2019.


References:

  1. Ocrevus (ocrelizumab) [Full Prescribing Information]. https://www.gene.com/download/pdf/ocrevus_prescribing.pdf. Accessed May 7, 2019.
  2. Ocrevus 300 mg concentrate for solution for infusion [Summary of Product Characteristics]. https://www.ema.europa.eu/documents/product-information/ocrevus-eparproduct-information_en.pdf. Accessed May 7, 2019.
  3. Reder A, et al. Baseline characteristics of the CHORDS study population: a phase III trial to evaluate the effectiveness and safety of ocrelizumab in patients with RRMS who had disease activity with prior disease-modifying therapies. Neurology. 2018;90(Suppl. 15):P6.370.
  4. Vollmer T, et al. Evaluation of shorter infusion times with ocrelizumab in patients with multiple sclerosis. Poster presented at: AAN Annual Meeting 2019; May 7, 2019; Philadelphia, PA, USA. Abstract P3.2-034.
  5. Hauser SL, et al. Long-term reduction in 48-week confirmed disability progression after 5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Poster presented at: AAN Annual Meeting 2019; May 7, 2019; Philadelphia, PA, USA. Abstract P3.2-054.
  6. Kobelt G, et al. New insights into the burden and costs of multiple sclerosis in Europe. Mult Scler. 2017;23:1123–1136.
  7. Giovannoni G, et al. Ocrelizumab treatment effect on upper limb function in ppms patients with disability: subgroup results of the ORATORIO study to inform the ORATORIO-HAND study design. Poster presented at: AAN Annual Meeting 2019; May 7, 2019; Philadelphia, PA, USA. Abstract P3.2-091.
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