At the cutoff date, the median treatment duration was 64.1 weeks (range 24.182.1) and 63.6 weeks (range 40.383.0) for patients in the OCR IV/SC and OCR SC/SC arms, respectively. == Table 1. were balanced across OCR IV/SC and OCR SC/SC arms (N = 118/118, 40.0 11.9/39.9 11.4 years, 59.3%/65.3% female, 89.0%/89.0% with RMS). The study demonstrated noninferiority of OCR SC 920 mg to OCR IV 600 mg for the primary end point AUCW112and also over the dosing interval for AUCW124(geometric mean ratios [90% CI] 1.29 [1.231.35] and 1.27 [1.211.34], respectively). At week 48, 111 of 118 (OCR IV/SC) and 114 of 118 (OCR SC/SC) had received OCR SC. A near-complete suppression of MRI activity was reported in OCR IV/SC and OCR S130 SC/SC: 0 of 113 and 0 of 113 patients had T1 lesions while 1 of 114 and 1 of 113 had 2 and 1 new/enlarging T2 lesions, respectively. Two patients (1.9%) in each arm had 1 relapse, and 1 patient (0.9%; OCR SC/SC) had 2 relapses. In both arms, rapid and sustained B-cell depletion was observed and serum neurofilament light chain reduction was comparable. Patients receiving at least 1 dose of OCR SC 920 mg in the OCR IV/SC and OCR SC/SC arms reported adverse events (AEs): 75.4% S130 and 86.4%, and serious AEs: 5.9% and 2.5%. The most frequently reported AEs were injection reactions (IRs, 51.5%); local and systemic IRs were experienced by 117 of 233 patients (50.2%) and 27 of 233 patients (11.6%), respectively. All IRs were mild/moderate; intensity and duration decreased with subsequent injections. == Discussion == The OCR SC formulation demonstrated noninferiority to OCR IV formulation regarding drug exposure, S130 providing comparable efficacy and safety and an additional treatment option for patients with multiple sclerosis. == Classification of Evidence == This study provides Class II evidence that a single SC injection of 920 mg of OCR achieves a noninferior 12-week S130 area under serum concentrationtime curve to that of 2 IV infusions of 300-mg OCR administered 2 weeks apart. == Trial Registration Information == ClinicalTrials.govIdentifierNCT05232825; submitted: January 27, 2022; first patient enrolled: May 3, 2022; available at:clinicaltrials.gov/study/NCT05232825?term=NCT05232825&rank=1. == Introduction == Ocrelizumab Rabbit Polyclonal to FRS3 (OCR) is an anti-CD20 monoclonal antibody and is the only high-efficacy disease-modifying therapy (DMT) approved for the treatment of patients with relapsing and primary progressive multiple sclerosis (PwRMS/PwPPMS).1,2As of March 2024, more than 350,000 patients had started OCR (resulting in more than 1,000,000 patient-years of follow-up), with over 10 years of safety and efficacy data from clinical trials.2,3OCR is administered as an initial dose of two 300-mg IV infusions 2 weeks apart, each lasting approximately 2.5 hours, with subsequent doses administered every 6 months as single 600-mg infusions over 2 or 3 3.5 hours.1,2 Accessing IV administration may be challenging for some patients, if they do not live close to an infusion center; some multiple sclerosis (MS) centers have limited or no IV infrastructure. For some patients, IV administration is not an option, and others may favor subcutaneous (SC) administration.4-6To deliver the clinical benefit of OCR and provide treatment flexibility, a new OCR formulation was developed for SC administration with the same twice-yearly schedule. OCR SC dose is coformulated with recombinant human hyaluronidase PH20 (rHuPH20; Halozyme Therapeutics, Inc., San Diego, CA), which allows for increased dispersion and absorption of SC-injected drugs by degrading hyaluronan at the local injection site, temporarily removing the barrier to bulk fluid flow, thereby permitting the rapid delivery of greater fluid volumes. 7rHuPH20 is currently used in SC coformulations with other approved monoclonal antibodies.8,9The OCR SC dose tested in this trial was selected based on safety, tolerability, and pharmacokinetic (PK) results of a phase 1b, dose-escalation,.