FDA Grants Breakthrough Therapy Designation to Treatment for Primary Progressive MS

Patient Expert

The MS community is one step closer to having an official medication for primary progressive MS (PPMS), a form of MS for which there are currently no approved treatments. While the relapsing MS community has 13 therapies from which to choose, patients with primary progressive disease have had few options.

Genentech and Roche announced that the Food and Drug Administration has granted Breakthrough Therapy Designation for the investigational medicine ocrelizumab (Ocrevus™) for the treatment of people with PPMS. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening disease and for which preliminary clinical evidence suggests that the drug may demonstrate substantial improvement over existing therapies. Remember that PPMS has no approved therapies.

Breakthrough Therapy Designation was granted to ocrelizumab based on positive results form a pivotal Phase III study (called ORATORIO) which showed treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo in patients with PPMS. Top-line results were of ORATORIO were presented at the 31th ECTRIMS conference in October 2015.

New data from the Phase III study will be presented at the ACTRIMS 2016 Forum on Friday, February 19th. The focus of this year’s ACTRIMS conference in New Orleans is “Progressive MS: From Bench to Bedside and Back.”

"Ocrelizumab is the first investigational medicine for MS to be granted Breakthrough Therapy Designation by the FDA," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "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."

Once Breakthrough Therapy Designation is granted, the FDA and drug company work together to determine the most efficient path forward to bring effective treatments to the patients who need them. Since 2012, the FDA lists 337 total requests for Breakthrough designation, 110 requests grants, and 181 requests denied, according to Friends of Cancer Research. As of February 11, 2016, the FDA had given 38 approvals to drugs designated as Breakthrough Therapies which indicates that this designation is not a guarantee of eventual marketing approval.

This is the 12th investigational drug for Genentech to receive breakthrough designation since 2013. Although a breakthrough therapy-designated medicine can be eligible for priority review, the sponsor (in this case Genentech) still needs to justify and formally request priority review within the Biologics License Application (BLA). A representative of Genentech tells me that they “plan to submit ocrelizumab data to the FDA in the first half of 2016 and are committed to working with the FDA to facilitate their review of the licensing application and potentially bring ocrelizumab to people with PPMS as quickly as possible.”

About ocrelizumab

Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. CD20-positive B cells are a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage, which can result in disability in people with MS. Based on preclinical studies, ocrelizumab binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.

In addition to ORATORIO, the Phase III clinical development program for ocrelizumab includes OPERA I and OPERA II, which are randomized, double-blind, double-dummy, global multi-center studies in people with relapsing forms of MS.

About the ORATORIO study in PPMS

ORATORIO is a Phase III, randomized, double-blind, global multi-center study evaluating the efficacy and safety of ocrelizumab compared with placebo in 732 people with PPMS.2 The primary endpoint of the study was time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks.

CDP measures a sustained protocol-defined increase in a patient’s Expanded Disability Status Scale (EDSS) score. The EDSS is based on a physical and neurological exam of eight systems throughout the body. The functional systems include vision, coordination, limb movement, strength, thinking abilities, bowel and bladder control, sensation and walking ability.

For more information:

Sorensen PS, Blinkenberg M. The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord. 2016 Jan; 9(1): 44–52. doi:  10.1177/1756285615601933