• Results from the Phase III study showed that subcutaneous (SC) injection was consistent with IV infusion and demonstrated near-complete suppression of relapse activity (97%) and MRI lesions (97.2%) through 48 weeks

• The twice-yearly, 10-minute SC injection has the potential to expand the usage of OCREVUS to treatment centres without IV infrastructure or with IV capacity limitations

• U.S. FDA and EMA accepted filings based on the data from OCARINA II, with EU approval anticipated mid-2024 and U.S. approval anticipated September 2024

Basel, 17 April 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today data from the Phase III OCARINA II study (S31.006) of OCREVUS (ocrelizumab), an investigational twice-yearly, 10-minute subcutaneous (SC) injection. Results showed near-complete suppression of clinical relapses and brain lesions in people with relapsing or primary progressive multiple sclerosis (RMS or PPMS) which reinforce the potential benefits of this investigational formulation. Treatment with OCREVUS SC led to rapid and sustained B-cell depletion in the blood. The data will be presented as an oral presentation at the 76th American Academy of Neurology (AAN) Annual Meeting taking place April 13-18 in Denver and has been recognised as an abstract of distinction by the AAN scientific committee.

"With a full year of data demonstrating near-complete suppression of relapse activity and minimal progression of lesion development, this 10-minute subcutaneous OCREVUS injection shows results that are consistent with the long-established benefits of intravenous OCREVUS," said Levi Garraway, M.D., Ph.D., Roche's chief medical officer and head of Global Product Development. "We look forward to continuing ongoing conversations with regulatory bodies worldwide to potentially bring an additional treatment option to more people living with MS, in a shorter injection time."

Updated, longer-term results showed that OCREVUS SC injection (920 mg; n=236; both treatment arms [OCR SC/SC and OCR IV/SC]) resulted in near-complete suppression of relapse activity (97.2% had no relapse during the treatment phase) and MRI up to 48 weeks with an ARR of 0.04, and most patients having no T1 gadolinium-enhancing (T1 Gd+) lesions and no new/enlarging T2 lesions. These lesion types are markers of active inflammation and burden of disease, respectively. Additionally, in exploratory patient reported outcome measures (n=52) patients reported a high level of satisfaction (92.3% were satisfied or very satisfied) and convenience (90.1% felt it was convenient or very convenient) with OCREVUS SC injection.

"Updated results from OCARINA II further underline the potential benefits of subcutaneous OCREVUS for patients with both relapsing and progressive forms of MS," said Scott Newsome, D.O., lead author, Johns Hopkins University School of Medicine. "Patients treated with subcutaneous OCREVUS experienced appropriate B-cell suppression and impressive near-complete suppression of new inflammatory disease activity. These results demonstrate the potential of subcutaneous OCREVUS as a treatment option that can be matched to the individual needs of people with MS and healthcare professionals."

Additional data continued to show that the safety profile of OCREVUS SC injection was consistent with the well-established safety profile of OCREVUS IV infusion. No new safety signals were identified for OCREVUS SC. The most common adverse events in the OCREVUS SC group were injection reactions (51.5% of all exposed patients), including erythema (34.8%; skin redness or irritation), pain (17.2%), swelling (9.4%) and pruritus (5.6%; skin itching), all of which were either mild or moderate and none of which led to treatment withdrawal. A total of seven serious AEs were experienced by three (2.6%) and four (3.4%) patients in the OCREVUS SC injection and IV infusion groups, respectively.

The OCARINA II abstract was selected as an abstract of distinction by the AAN, based on the quality of the study and the interest to the neurology community.

The twice-yearly, 10-minute SC injection has the potential to expand the usage of OCREVUS to treatment centres without IV infrastructure or with IV capacity limitations. Data from the Phase III OCARINA II trial were submitted to health authorities around the world following the first presentation of these results during ECTRIMS-ACTRIMS 2023. Both the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) have accepted Roche's submissions, with a target decision date of mid-2024 for the EMA and September 2024 for the FDA.

More than 300,000 people with MS have been treated with OCREVUS IV globally. OCREVUS IV is approved in more than 100 countries across North America, South America, the Middle East, Eastern Europe, Asia, Australia, Switzerland, the United Kingdom and the EU.

Roche is committed to advancing innovative clinical research programmes to broaden the scientific understanding of MS, further reducing disability progression in RMS and PPMS and improving the treatment experiences for those living with the disease. There are more than 30 ongoing OCREVUS clinical trials designed to help us better understand MS and its progression.

About the subcutaneous formulation of OCREVUS (ocrelizumab)
The investigational subcutaneous (SC) formulation combines OCREVUS with Halozyme Therapeutics' Enhanze drug delivery technology.

OCREVUS is a humanised monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, suggesting that important functions of the immune system may be preserved.

The Enhanze drug delivery technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that locally and temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – in the SC space. This increases the permeability of the tissue under the skin, allowing space for large molecules like OCREVUS to enter, and enables the SC formulation to be rapidly dispersed and absorbed into the bloodstream.

OCREVUS IV is the first and only therapy approved for both RMS (including relapsing-remitting MS [RRMS] and active, or relapsing secondary progressive MS [SPMS], in addition to clinically isolated syndrome [CIS] in the U.S.) and PPMS. OCREVUS IV is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.