The Genentech agent, which is approved for patients with relapsing-remitting multiple sclerosis, showed no new safety signals in a comparison between conventional and shorter infusion times.
Amy P. Ross, APN, MSN, CNRN, MSCN
Results from the ENSEMBLE PLUS study of ocrelizumab (Ocrevus; Genentech) revealed that the frequency and severity of infusion-related reactions (IRR) are comparable between the conventional, approved 3.5-hour infusion time versus shorter infusion times nearing 2 hours in patients with relapsing-remitting multiple sclerosis (MS).1
The data, presented at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting, May 26-29, 2020, showed that 67 (23.1%) of the 291 patients and 71 (24.6%) of the 289 patients randomized to conventional and shorter infusion groups, respectively, had IRRs.
More specifically, 17.9% and 31.0% of patients in the convention and shorter infusion groups, respectively, experienced throat irritation, while 25.4% and 23.9% experienced fatigue, respectively. Most IRRs were deemed mild or moderate and >98% of all IRRs were resolved without sequelae in both groups.
Laryngeal inflammation, occurring after the second randomized dose, was the only reported severe IRR in the conventional group, while fatigue, occurring after the first randomized dose was the only severe IRR for the shorter duration group. Researchers deemed none of the IRRs to be life threatening, serious, or fatal.
During the first randomized dose, 14 (4.8%) and 25 (8.7%) patients in the conventional and shorter infusion groups had IRRs leading to infusion interruption or slowing, respectively. No new safety signals were detected in the study.
Amy Perrin Ross, APN, MSN, CNRN, MSCN, coordinator, Neuroscience Program, Loyola University Medical Center, and colleagues, conducted ENSEMBLE-PLUS, a randomized, double-blind substudy of the single-arm ENSEMBLE study (NCT03085810) to investigate the safety profile of ocrelizumab when administered over a shorter infusion time.
Patients with early-stage relapsing remitting MS (aged 18 to 55 years; treatment-naïve; disease duration ≤3 years; Expanded Disability Status Scale [EDDS] score, 0—3.5) received ocrelizumab 600-mg infusions every 24 weeks for 192 weeks in ENSEMBLE. In ENSEMBLE-PLUS, ocrelizumab 600 mg was administered in both the approved infusion time and 2-hour infusion groups. Each patient had the same initial infusion (2 x 300 mg) duration times.
Ocrelizumab, originally approved in 2017 for the treatment of relapsing forms of MS, including clinically isolated syndrome, as well as secondary progressive and primary progressive disease, received approved updates by the FDA in early January regarding new information about infusion reactions, vaccinations, and risks in specific patient populations.2
Months later, Genentech announced that both the FDA and EMA had accepted supplemental applications for review for a new 2-hour ocrelizumab infusion that would be administered 2 times per year for those with relapsing or primary progressive MS. The supplemental biologics license application (sBLA) was accepted by the FDA based on data from the ENSEMBLE-PLUS study.3
The company also noted that the FDA and European Commission are expected to make decisions on these applications by the end of the year.
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1. Ross AP, Berger T, Bermel R, et al. Shorter infusion time of ocrelizumab: primary results from the ENSEMBLE-PLUS study in patients with relapsing-remitting multiple sclerosis. Int J MS Care. 2020;22(2 Suppl).
2. Drug Safety-related Labeling Changes (SrLC). US FDA website. January 15, 2020. accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm. Accessed January 15, 2020.
3. US FDA and EMA accept applications for Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time [press release]. Basel, Switzerland: Genentech; Published April 20, 2020. Accessed April 20, 2020. globenewswire.com/news-release/2020/04/20/2018330/0/en/US-FDA-and-EMA-accept-applications-for-Roche-s-OCREVUS-ocrelizumab-shorter-2-hour-infusion-time.html
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