Long-Awaited Multiple Sclerosis Drug Wins FDA Approval

The multiple sclerosis (MS) community eagerly awaited the March 28 FDA approval of ocrelizumab (Ocrevus) for treating relapsing and primary progressive forms of MS.

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, which are thought to be a key contributor to myelin and axonal damage. It is the first and only medication approved to treat both relapsing MS (RMS) and primary progressive MS (PPMS).

The approval was based on the identical RMS phase 3 studies OPERA 1 and OPERA 2, as well as the separate PPMS phase 3 trial ORATORIO.

The randomized, double-blind, double-dummy, global multi-center OPERA 1 and OPERA 2 studies, evaluated the safety and efficacy of ocrelizumab in 1656 patients with RMS. Patients were administered either 600 mg of ocrelizumab by intravenous infusion every 6 months or 44 mcg of interferon beta-1a administered by subcutaneous injection 3 times per week.

In the randomized, double-blind, global multi-center ORATORIO study, investigators evaluated the safety and efficacy of 600 mg of ocrelizumab administered by intravenous infusion every 6 months—–given as two 300-mg infusions 2 weeks apart––compared with placebo in 732 patients with PPMS.

In OPERA 1 and 2, ocrelizumab demonstrated superior efficacy compared with high-dose interferon beta-1a (Rebif) in reducing relapses per year by nearly half, slowing the worsening of disability, and significantly reducing magnetic resonance imaging (MRI) lesions over the 2-year controlled treatment period.

Patients administered ocrelizumab showed a 46% and 47% relative reduction in the annualized relapse rate compared with interferon beta-1a over the 2-year period, respectively. There was a 40% relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with interferon beta-1a in a pooled analysis of both OPERA studies.

Additionally, there was a 94% and 95% relative reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a, respectively, and a 77% and 83% relative reduction in the total number of new and/or enlarging T2 lesions compared with interferon beta-1a, respectively.

In the ORATORIO study, ocrelizumab was the first and only treatment to significantly slow disability progression and reduce signs of disease activity in the brain (MRI lesions) compared with placebo with a median follow-up of 3 years.

Patients with PPMS who received ocrelizumab achieved a 24% relative risk reduction in CDP sustained for at least 12 weeks compared with placebo; a ­0.39 cm³ mean change in volume of brain hyperintense T2 lesions compared with a 0.70 cm³ mean change in volume of placebo-treated patients over 120 weeks; and a 25% relative risk reduction in the proportion of patients with 20% worsening of the timed 25-foot walk confirmed at 12 weeks.

“The FDA’s approval of Ocrevus is the beginning of a new era for the MS community and represents a significant scientific advance with this first-in-class B cell targeted therapy,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “Until now, no FDA-approved treatment has been available to the primary progressive MS community, and some people with relapsing forms of MS continue to experience disease activity and disability progression despite available therapies. We believe Ocrevus, given every 6 months, has the potential to change the disease course for people with MS, and we are committed to helping those who can benefit gain access to our medicine.”

The most common ocrelizumab-induced adverse events (AEs) in all the studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.

Potential serious AEs included infusion reactions, infections, and malignancies where only routine screening is required based on age and medical history, according to the release.

“This is an exciting day for everyone touched by MS, a disease that strikes in the prime of a person’s life when she or he may be starting a career or family,” June Halper, MSN, APN-C, MSCN, FAAN, CEO at the Consortium for MS Centers, said in the release. “We have eagerly awaited the FDA approval of Ocrevus because it not only offers a new, highly efficacious treatment option for people with relapsing multiple sclerosis, but it is also the first disease-modifying therapy indicated for primary progressive multiple sclerosis, a highly disabling type of this chronic disease. For many people living with MS, this FDA approval is a source of hope.”

Ocrelizumab is administered by intravenous infusion every 6 months. The first dose is administered as two 300-mg infusions given 2 weeks apart. Subsequent doses are administered as single 600-mg infusions. Ocrelizumab will be available in the United States within 2 weeks.