FDA Grants ‘Breakthrough Therapy’ Designation to Genentech’s Ocrelizumab for PPMS

Genentech recently announced that the U.S. Food and Drug Administration (FDA) granted its investigational medicine ocrelizumab, a potential treatment for primary progressive multiple sclerosis (PPMS), Breakthrough Therapy Designation based on positive Phase 3 clinical trial results showing that ocrelizumab significantly reduced disability progression and other disease activity markers compared to placebo.

The FDA designation is intended to speed the development and agency review of medicines aiming to treat serious and life-threatening diseases. Ocrelizumab is the first medicine to show positive pivotal trial results in both PPMS and relapsing MS, a more common form of the disease.

Currently, there are no approved treatments for PPMS, a debilitating disease form characterized by slow onset and steadily worsening symptoms. About 10 percent of the estimated 2.3 million people worldwide with MS have this form of the disease.

“Ocrelizumab is the first investigational medicine for MS to be granted Breakthrough Therapy Designation by the FDA,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “With no approved treatments for primary progressive MS, ocrelizumab has the potential to address an important unmet need. We are committed to working with the FDA to bring ocrelizumab to people with primary progressive MS as quickly as possible.”

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, a type of immune cell thought to contribute to the myelin (a nerve cell insulator) and nerve cell (axonal) damage that results in MS. Preclinical studies showed that ocrelizumab works by binding to CD20 cell surface proteins expressed on certain B cells, although not to stem cells or plasma cells, so as to preserve key immune system functions.

The pivotal, multicenter and doubled-blinded Phase 3 clinical trial, called ORATORIO, is investigating the efficacy and safety of ocrelizumab compared with placebo in 732 people with PPMS. Participants randomly received ocrelizumab intravenously in two infusions of 300 mg every 14 days in each treatment cycle, or received placebo, with the primary endpoint being time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks. CDP was measured using the Expanded Disability Status Scale, a physical and neurological exam that covers vision, coordination, limb movement, strength, thinking abilities, bowel and bladder control, sensation, and walking ability.

ORATORIO’s start date was March 2011, and the trial is expected to be completed in November 2017.

Top-line results from the trial were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October 2015, and showed a superior reduction in disease progression at 12 weeks in the treatment group as compared to the placebo group (24 percent),  as well as a 25 percent reduction in the risk of CDP at 24 weeks, and a significant reduction of 29 percent in the progression rate of walking time. Ocrelizumab was also found to significantly reduce brain lesions (by 3.4 percent) in comparison to a placebo therapy, and to promote a reduction in whole brain volume loss by 17.5 percent (week 24 to week 120).

Genentech said in its announcement that it plans to pursue marketing authorization for ocrelizumab as both a PPMS and relapsing MS treatment, and will submit data from its three Phase 3 studies to the FDA by June 2016. In addition to ORATORIO, ocrelizumab was tested in two large-scale, pivotal trials involving relapsing MS patients, called OPERA I and OPERA II.

Genentech is a member of the Roche Group and is headquartered in San Francisco. Ocrevus is the company’s proprietary name for its ocrelizumab treatment.