Ocrelizumab Holds Benefit for Relapsing MS Patients With Prior Suboptimal DMT Response

Two-year findings from the phase 3b CHORDS study (NCT02637856) demonstrated that patients with relapsing-remitting multiple sclerosis (RRMS) see benefits from ocrelizumab (Ocrevus; Genentech) treatment despite having a suboptimal response to previous disease-modifying therapy (DMT).¹

The modified intention-to-treat (mITT) population included 576 patients, 48.1% of which were free of all protocol-defined events following treatment with ocrelizumab 600 mg. More specifically, freedom from relapse, gadolinium-enhancing (GdE) lesions, and new/enlarging T2 lesions occurred in 89.6%, 95.5%, and 59.5% of patients, respectively.

Presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020 by Bianca Weinstock-Guttman, MD, of Buffalo General Medical Center, the data also showed no confirmed disability progression (CDP) in 89.6% of patients over 96 weeks for those treated with ocrelizumab.

Weinstock-Guttman and colleagues found similar results in those who received 1 versus >1 prior DMT (50.9% vs 44.5%) for individual events (relapse: 90.% vs 89.2%; T1 GdE lesion: 95.8% vs 95.1%; new/enlarging T2 lesion: 61.4% vs 57.1%; 24-week CDP: 90.9% vs 87.9%). Notably, the adjusted annualized relapse rate (ARR) assessed in the ITT population over 96 weeks was 0.046.

Stable changes in Expanded Disability Status Scale (EDSS), defined as a <1-point change, occurred in 61.5% of the population. Improvements in EDSS, defined as ≥1-point decrease, occurred in 22.7% of patients. There were no deaths or new safety signals observed.

Among the 608 patients in the ITT population, the mean time since diagnosis was 4.2 years (standard deviation [SD], 3.03). The most frequently used DMTs prior to enrollment included glatiramer acetate (49.3%), dimethyl fumarate (35.4%) and fingolimod (20.1%).

Additional data on ocrelizumab from the phase 3b CASTING study (NCT02861014) were also presented.²

A pair of datasets from that study suggested that patients treated with the agent experienced high rates of no evidence disease activity (NEDA) status regardless of prior DMT exposure. Furthermore, after the 2-year treatment period, 492 of 658 patients (74.8%) qualified for NEDA status (with MRI re-baselined at Week 8 of treatment). The highest rates of NEDA were observed in those who were enrolled due to only MRI activity (80.6%). Those with only relapses achieved NEDA at a rate of 75.1% compared with 70.5% in patients with both MRI and relapse activity.

Genentech announced in April that the FDA accepted its supplemental biologics license application for a version of ocrelizumab with a shorter administration time for the treatment of relapsing and primary progressive MS. The sNDA was accepted by the FDA based on data from the ENSEMBLE PLUS study, a double-blind, prospective sub-study to the open-label, single-arm, phase 3b ENSEMBLE (NCT03085810) trial.³

The FDA also approved updates to the drug label of ocrelizumab in January, reflecting new information about infusion reactions, vaccinations, and risks in specific patient populations.⁴

For more coverage of MS Virtual 2020, click here.

REFERENCES

1. Weinstock-Guttman B, Bermel R, Cutter G, et al. Ocrelizumab treatment in patients with RRMS who had suboptimal response with one or more prior disease-modifying therapies: CHORDS 2-year results. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0221.

2. Wiendl H, Comi G, Oreja-Guevara C, et al. Ocrelizumab Phase IIIb efficacy from CASTING: 2-year NEDA (MRI re-baselined) subgroup rates in RRMS patients with a suboptimal response to prior DMTs. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0219.

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 September 21, 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

4. Drug Safety-related Labeling Changes (SrLC). US FDA website. January 15, 2020. Accessed September 21, 2020. accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm.