FDA Approves Ocrelizumab Shorter 2-Hour Infusion for MS


Data used from the ENSEMBLE PLUS study showed a comparable frequency of infusion reactions between those who received the 2-hour infusion and the 3.5-hour infusion.

Levi Garraway, MD, PhD

The FDA has approved a shorter 2-hour infusion time for ocrelizumab (Ocrevus; Genentech), dosed twice-yearly for patients with relapsing or primary progressive multiple sclerosis (MS) who have not experienced any prior serious infusion reactions (IRs).1

The basis for the approval was from the randomized, double-blind ENSEMBLE PLUS study, a prospective substudy to the open-label, single-arm, phase 3b ENSEMBLE (NCT03085810) trial. Results showed a similar frequency and severity of IRs for a 2-hour ocrelizumab infusion time compared to the previously approved 3.5-hour time in patients with relapsing-remitting MS (RRMS).

“More than 170,000 people with MS have been treated with Ocrevus—the only approved B-cell therapy with a twice-yearly dosing schedule—and it is the most prescribed MS medicine in the US,” Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Roche, said in a statement.

Patients included in the study received the first dose using the approved dosing schedule (2, 300-mg intravenous [IV] infusions separated by 2 weeks) and the second or later doses (600-mg IV infusion) through the shortened administration time.

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The primary end point of the study was the proportion of patients with IRs following the first randomized 600-mg infusion, with frequency and severity assessed during infusion and 24-hours after. Researchers found that the frequency of IRs was comparable to between those who received the 2-hour infusion (24.6%) and those who received the 3.5-hour infusion (23.1%).

More than 98% of the IRs were resolved within both groups without complication, and IRs were mild or moderate in nature. There were no discontinuations due to an IR and no new safety signals observed.

"We constantly strive to improve the experience that patients and their physicians have with our medicines, and we believe people with relapsing and primary progressive MS will find the shorter 2-hour Ocrevus infusion time to be more convenient,” Garraway added.

The FDA accepted the supplemental biologics license application (sBLA) for the shorter infusion ocrelizumab in April.2 Ocrelizumab was approved as the first of its kind treatment of primary progressive MS in 2017.

In January, the FDA updated the drug’s label with new safety information, including additions to the possible infusion-related reactions and information regarding the need for immunizations, revisions to pregnancy risk summary, and updates to the Patient Counseling section.3

In February, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 27-29, 2020, in West Palm Beach, Florida, data were presented from an open-label assessment of the OPERA 1 (NCT01247324) and OPERA 2 (NCT01412333) studies, which showed that those with relapsing MS who initiated ocrelizumab treatment earlier reported better rates of 24-week confirmed disability progression (CDP24) and relapse compared with those who received initial interferon treatment.4

Later in the year, in November, results from the ongoing, long-term open-label extension of the phase 3 ORATORIO study (NCT01194570) demonstrated that earlier and continuous treatment with ocrelizumab provided sustained benefits on measures of disease progression in patients with primary progressive multiple sclerosis compared with patients switching from placebo.5

The proportion of patients with significantly lower Expanded Disability Status Scale scores was higher in those receiving continuous ocrelizumab (64.8%) than in those switching to ocrelizumab (51.7%), a difference of 13.1% (95% CI, 4.9–21.8; P = .0018) after the full follow-up. Similar results were seen on 9-hole peg test (30.6% vs 43.1%; difference, 12.5 [95% CI, 4.1–20.9]; P = .0035), timed 25-foot walk (63.2% vs 70.7%; difference, 7.5 [95% CI, –0.3 to 15.2]; P = .058), and composite progression (73.2% vs 83.3%; 95% CI, 3.6–16.6; P = .0023). Additionally, time to require a wheelchair was observed in 11.5% of those who received continuous ocrelizumab treatment compared to 18.9% of those who switched, for a difference of 7.4% (95% CI, 0.8–13.9; P = .0274).

1. FDA approves Genentech’s Ocrevus (ocrelizumab) shorter 2-hour infusion for relapsing and primary progressive multiple sclerosis. News release. Genentech. December 14, 2020. Accessed December 14, 2020. https://www.businesswire.com/news/home/20201214005766/en/FDA-Approves-Genentech%E2%80%99s-Ocrevus-ocrelizumab-Shorter-2-Hour-Infusion-for-Relapsing-and-Primary-Progressive-Multiple-Sclerosis
2. US FDA and EMA accept applications for Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time. News release. Genentech; Published April 20, 2020. Accessed December 14, 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
3. Drug Safety-related Labeling Changes (SrLC). US FDA website. January 15, 2020. Accessed December 14, 2020. accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm.
4. Hauser SL, Kappos L, Giovannoni G, et al. Long-term reduction of relapse rate and confirmed disability progression after 6 years of ocrelizumab treatment in patients with relapsing MS. Presented at 2020 ACTRIMS forum. February 27-29, 2020; West Palm Beach, Florida. Abstract P064.
5. Wolinsky JS, Arnold DL, Brochet B, et al. Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomized, placebo-controlled, phase 3 trial. Lancet Neurol. Published online October 29, 2020. doi: 10.1016S1474-4422(20)30342-2
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