In late April, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a recommendation for approval for Ocrelizumab (OCREVUS®) in a subcutaneous (s.c.) administration form. As with the intravenous (i.v.) administration already approved since 2018, the recommendation for approval applies to adults with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). It is expected that the s.c. formulation of Ocrelizumab will be available in pharmacies around the time this blog post is published.
The recommendation for approval is based on the results of the phase-Ib dose-finding study OCARINA I. In this study, 920 mg of Ocrelizumab s.c. was identified as the “optimal” dosage. The B-cell depletion with 920 mg s.c. was comparable to the established i.v. administration. The depletion occurred quickly and was well tolerated, no new safety concerns arose.
In the follow-up study OCARINA II, the s.c. formulation of OCREVUS proved to be non-inferior to the i.v. application over a period of 12 weeks. The administration of Ocrelizumab 920 mg s.c. led to a similar overall exposure as Ocrelizumab 600 mg i.v. in the first 12 weeks, thus meeting the primary study endpoint and proving the non-inferiority of the subcutaneous formulation. With the s.c. application of 920 mg, almost complete suppression of disease activity over 48 weeks was achieved in the course of the study. 97.2% of study patients remained relapse-free, the annual relapse rate (ARR) was 0.04 (= one relapse in 25 years). Thus, two comparable options for treatment with Ocrelizumab are now available to people affected by MS.
In practice, the s.c. injection of Ocrelizumab is administered into the abdomen. The administration is carried out by medical professionals and takes approximately 10 minutes.
Ultimately, the OCARINA studies, with their positive results, reflect a general trend away from intravenous administration of biologics towards subcutaneous administration of active ingredients. In other specialties such as dermatology or rheumatology, the administration of highly effective medications has predominantly been subcutaneous for some time. Therefore, it is not surprising that more and more highly effective MS medications are now also available in subcutaneous formulations. Some time ago, subcutaneous Natalizumab (Tysabri®) was approved, which was very well received by patients and now the antibody Ocrelizumab is also available in a subcutaneous formulation. Ofatumumab (Kesimpta®), an antibody also directed against B cells for the treatment of active MS, was primarily developed as a subcutaneous formulation.
Therefore, there is already experience with subcutaneous application both from other indication areas and from MS therapy, which is not only based on study results but also on the practical experience of i.v. administration is not inferior.
Subcutaneous administration has undeniable advantages. Even if it (like with Ocrelizumab) is performed by medical professionals, the time advantage is immense. This is not only beneficial for patients, who no longer have to spend several hours in the infusion outpatient department, but also poses significantly lower logistical demands on the medical staff. The time-consuming process of inserting an infusion needle is eliminated, as is the need for prolonged monitoring. The space requirements in practices and clinics are also reduced.
Therefore, the availability of subcutaneous Ocrelizumab is good news and promises practical advantages. It is nice that it has been possible to maintain a therapy-free interval of 6 months with the s.c. formulation. From my experience, these rare therapeutic interventions are indeed a real gain for the quality of life of our patients.
