The Results of the PK Bridging Study, OCARINA II, was the basis of the FDA approval of Ocrevus Zunovo⁶

*CCOD: March 10, 2023
^aExploratory radiologic objectives included total T1 Gd+ lesions at Weeks 48 and 96, and N/E T2 lesions at Weeks 8, 48 and 96; ^bExploratory clinical objectives included annualized PDR rate by Weeks 24, 48 and 96 in patients with RMS, and change in EDSS from baseline at Weeks 48, 72 and 96; ^cExploratory PD objectives included the proportion of patients achieving CD19+ B-cell level ≤5 cells/μL at Weeks 48 and/or 96; ^dAssessed via the Treatment Administration Satisfaction Questionnaires (TASQ) which is a self-reported patient instrument, designed to assess satisfaction with and impact of 2 different routes of treatment administration (IV and SC)3; ^eThe 920 mg OCR SC dose was established as the recommended dose in the OCARINA I study (NCT03972306); ^fThe first dose of OCR IV was administered as two 300 mg IV infusions given 2 weeks apart; ^gThe screening phase in patients with RMS and PPMS took place before baseline MRI readings and patients were randomized 1:1 between the two arms; ^hCut-off date is when the last patient completes 12 weeks. ⁱTwo patients from the OCR SC/SC arm were excluded from the PK-evaluable analysis set due to an incomplete SC dose and an impossible concentration-time profile. Two patients from the OCR IV/SC arm were excluded from the PK-evaluable analysis set due to a delay in the second IV infusion and a missing second IV infusion; ^jEstimated mean exposure for AUC or Cmax; Ocrevus IV 600 mg was administered as two 300 mg IV infusions given 14 days apart. ^kThe geometric mean ratio (GMR) is calculated from the geometric mean values for each treatment arm. The geometric mean is used because PK parameters have a log-normal distribution rather thana normal distribution. ^lGMR and two-sided 90% CI of SC vs IV between baseline and Week 12. Non-inferiority would be established if the lower end of the two-sided 90% CI is >0.8; the non-inferiority limit of 0.8 corresponds to a maximal 20% loss in AUC for the SC administration compared with IV, as recommended in the regulatory guidance documents for demonstration of bioequivalence for PK bridging.^{6,7 m}Study 4 refers to the OCARINA II Phase 3, PK noninferiority study comparing OCR SC 920 mg vs OCR IV 600 mg; ⁿStudy 1 and 2 refer to the (OCR IV) OPERA I and II Phase 3 clinical trials in patients with RMS; ^oStudy 3 refers to the (OCR IV) ORATORIO Phase 3 clinical trial in patients with PPMS.
ADA, antidrug antibody; AE, adverse event; AUC, area under the serum concentration–time curve; CCOD, clinical cut-off date; CI, confidence interval; Cmax, maximum serum concentration; EDSS, Expanded Disability Status Scale; Gd+, gadolinium-enhancing; GMR, geometric mean ratio; IV, intravenous; MRI, magnetic resonance imaging; MS, multiple sclerosis; N/E, new/enlarging; OCR, ocrelizumab; PD, pharmacodynamic; PDR, protocol-defined relapse; PK, pharmacokinetic; PPMS, primary progressive multiple sclerosis; PRO, patient-reported outcome; rHuPH20, recombinant human hyaluronidase PH20; RMS, relapsing multiple sclerosis; SC, subcutaneous; Tmax, time to maximum concentration; USPI, United States Prescribing Information; W, week.
1. Newsome SD et al. CMSC 2024; Nashville, TN; May 30, 2024; Presentation DMT06. 2. Thompson AJ, et al. Lancet Neurol 2018;17:162–173. 3. Doll H, et al. J Patient Rep Outcomes. 2021;5(1):45. 4. Newsome SD et al. ECTRIMS-ACTRIMS 2023; Milan, Italy; October 11-13, 2023. P370. 5. Newsome SD et al. AAN 2024; Denver, CO; April 13 -18, 2024; Poster S31.001. 6 . Ocrevus Zunovo™ [package insert]. Genentech; South San Francisco, CA. 7. Food and Drug Administration. Bioavailability studies submitted in NDAs or INDs – General considerations. April 2022. Available from: https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents/​bioavailability-studies-submitted-ndas-or-inds-general-considerations. Accessed April 12, 2024.

All patients who received at least one dose of ocrelizumab SC were included in the OCR SC all-exposure group, regardless of which treatment arm they were randomized to. The safety follow-up phase lasted 24 weeks after the last dose^1,a-e

^aAll patients who received at least one dose of ocrelizumab SC were included in the OCR SC all-exposure group, regardless of which treatment arm they were randomised to. ^bReported terms of AEs were encoded using MedDRA version 28.0. ^cGrades were based on NCI CTCAE v5.0. ^dGrade 3 AEs included chest pain, physical deconditioning, COVID-19, pneumonia bacterial, intervertebral disc protrusion, joint instability, cytopenia, eye pain, lymphocyte count decreased, lung neoplasm, malignant melanoma, MS pseudo relapse, abortion spontaneous, anxiety, renal disorder, Bartholin’s cyst, cervix cerclage procedure, with n=1 in all instances. One patient could have presented with more than one AE. ^eGrade 4 AE of suicidal behaviour with attempted self-harm and parallel Grade 3 nonserious AE of increased anxiety; both events resolved.
AE, adverse events; IR, injection reaction; MedDRA, Medical Dictionary for Regulatory Activities; MS, multiple sclerosis; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; OCR, ocrelizumab; SC, subcutaneous.
1. Newsome SD, et al. ECTRIMS 2025; Barcelona, Spain; September 24-26, 2025. Poster P307.

^aClinical cutoff: 7 August 2025.^bAll patients who received at least one dose of ocrelizumab SC were included in the OCR SC all-exposure group, regardless of which treatment arm they were randomised to. ^cProportions of patients with at least one symptom are calculated based on the number of patients in the treatment arm. Each IR may have multiple symptoms. Multiple occurrences of an IR symptom in one patient at one injection (or overall) were counted once for that injection (or overall). ^dMost local IRs had a duration <1 day at all injections; injection 1 (19/27, 70.4%), injection 2 (11/20, 55.0%), injection 3 (16/25, 64.0%), injection 4 (14/18, 77.8%) and injection 5 (4/7, 57.1%). ^eForty-three patients had erythema at injection 1 and 17 patients had erythema at injection 5. ^fFive patients had swelling at injection 1 and three patients had swelling at injection 4. ^gPercentage of patients with ≥1 IR for selected injection is calculated as number of patients with IRs at this injection (n) divided by the number of patients who received the injection per treatment group (N). The reported most extreme NCI CTCAE grade of IRs is used to display the severity of IRs. If patients experience multiple IRs for one injection, the maximum most extreme NCI CTCAE grade is displayed per patient and injection. Injection 1 corresponds to Dose 2 for patients randomized to the IV/SC treatment arm and Dose 1 for patients randomized to the SC/SC treatment arm. Subsequent injections correspond to subsequent doses. ^hOnly patients in the SC/SC arms received a 5th injection. ⁱWhere treatment for IRs was administered, the medications were standard of care treatments, including mostly analgesics (e.g., ibuprofen or paracetamol), and oral or topical antihistamines (e.g., diphenhydramine or cetirizine). ^jCCOD: December 4, 2023. ^k10 min refers to IRs occurring during injection and the duration of the SC injection, which is approximately 10 minutes. ^lExcept bruising, which occurred >1 hour after injection.

CCOD, clinical cut-off date; IR, injection reaction; IV, intravenous; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; OCR, ocrelizumab; SC, subcutaneous.
Ocrevus Zunovo [package inset]. Genentech USA, Inc.; South San Fransico, CA. 2. Newsome SD, et al. ECTRIMS 2025; Barcelona, Spain; September 24-26, 2025. Poster P307. 3. Newsome SD et al. CMSC 2024; Nashville, TN; May 30, 2024; Presentation DMT06.

• Use of non-validated, investigator-designed surveys, which may limit comparability across studies.
• Self-selection bias: patients who agreed to switch may have been more motivated or predisposed to favor the SC route. The high rate of convenience-driven transitions (91%) supports this.
• Disease stability assessed by patient perception rather than objective measures (MRI, relapse adjudication, EDSS).
• Limited demographic diversity (78.6% White/Caucasian), which may affect generalizability.
• Small sample size for subgroup analyses, particularly the prior IV cohort (n = 56).

1.Holian, A. et al. Presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026; February 5-7, 2026; San Diego, CA, USA. 2. Holian, A. et al. Presented at the National Association of Specialty Pharmacy (NASP) Annual Meeting 2025; September 14-17, 2025; Denver, CO, USA.

IV, intravenous; MS, multiple sclerosis; PK, pharmacokinetic; SC, subcutaneous.
1.Ocrevus Zunovo [package insert]. Genentech USA, Inc.; South San Francisco, CA. 2. Locke K, et al. Drug Deliv 2019;26:98-106. 3. FDA. Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process. Available at https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents/​q5e-comparability-biotechnologicalbiological-products-subject-changes-their-manufacturing-process. Accessed May 14, 2024. 4. Xu Z, et al. Clin Pharmacol Ther. 2023;113(5):1011-1029. 5. Newsome SD, et al. AAN 2024; Denver, CO; April 13 -18, 2024;Poster S31.001. 6. Holian, A. et al. Presented at the National Association of Specialty Pharmacy (NASP) Annual Meeting 2025; September 14-17, 2025; Denver, CO, USA.