Ocrelizumab Granted “Breakthrough Therapy Designation” for Primary-Progressive MS by FDA

esignation Can Expedite Review Once Submitted For FDA Approval 

Genentech, a member of the Roche Group, has announced that the experimental therapy ocrelizumab has been granted “Breakthrough Therapy designation” by the U.S. Food and Drug Administration (FDA) for the treatment of people with primary-progressive MS. This designation means that once Genentech files for approval of ocrelizumab to treat primary-progressive MS, the review process can be expedited. According to a February 16 press release, Genentech plans to pursue marketing approval for both primary-progressive MS and relapsing multiple sclerosis, and will submit data from three phase III studies to the FDA in the first half of 2016.

“We are encouraged by this news and look forward to following the FDA’s actions regarding ocrelizumab,” says Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer at the National MS Society. “People with progressive MS need solutions and we are hopeful that this is the first of many treatments that will be developed for this form of MS.”

Breakthrough Therapy designation can expedite the development and review of therapies intended to treat a serious condition when clinical evidence indicates that the treatment may demonstrate substantial improvement over available therapy. The designation was granted to ocrelizumab based on phase III trial results presented at the European Committee for Treatment and Research in MS in 2015. Compared to placebo, ocrelizumab significantly reduced the risk of progression of clinical disability by 24% in 732 people with primary-progressive MS.

Ocrelizumab is a monoclonal antibody that binds to a molecule (CD20) on the surface of immune cells called B cells, and depletes them from circulation. B cells have several functions including making antibodies, and they may play a role in immune-system mediated damage to brain and spinal cord tissues in MS. Ocrelizumab is administered by intravenous infusion every 6 months. There currently are no FDA-approved disease-modifying therapies to treat primary progressive MS, which is characterized by steady worsening of neurologic functioning, without any distinct relapses or attacks, or periods of remission.

Frequently Asked Questions Related to “Breakthrough Therapy” Designation of Ocrelizumab to Treat Primary-Progressive MS

Q: What is Breakthrough Therapy designation?
A: The Food and Drug Administration has developed four approaches to making treatments available as rapidly as possible when treatments are the first available treatment or if the therapy has advantages over existing treatments. Breakthrough Therapy designation can expedite the development and review of therapies intended to treat a serious condition when clinical evidence indicates that the treatment may demonstrate substantial improvement over available therapy. This designation makes the treatment eligible for all Fast Trackdesignations, intensive guidance on an efficient drug development program, and organizational commitment involving senior managers. It does not make the treatment automatically eligible for priority review, which means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review).

Q: Does this mean that ocrelizumab is approved to treat primary-progressive MS?
A: No, this means that once Genentech files with the FDA for approval of ocrelizumab to treat primary-progressive MS, the review process can be expedited. According to a February 16 press release, Genentech plans to pursue marketing approval for both primary-progressive MS and relapsing multiple sclerosis, and will submit data from three phase III studies to the FDA in the first half of 2016.

Q: Will ocrelizumab be approved to treat secondary-progressive MS?
A: At this point, Genentech plans to pursue marketing approval for both primary-progressive MS and relapsing multiple sclerosis. Relapsing MS includes people with secondary-progressive MS who are experiencing relapses. Ocrelizumab reduced relapse rates by 46% to 47% after two years compared to the established MS treatment, Rebif^® (interferon beta-1a, EMD Serono) in two phase III studies in people with relapsing MS. Ocrelizumab has not been studied so far in people with secondary-progressive MS who are not experiencing relapses. Breakthrough designation only applies to primary-progressive MS.

Q: When will ocrelizumab become available?
A: It is not possible to say if or when ocrelizumab may become available.  The company has stated plans for applying for regulatory approval of ocrelizumab in the first half of 2016.  Even with an expedited review, the timeline for successful marketing approval depends on many variables, such as whether the application is accepted by the FDA or whether the agency requests additional information before the application is deemed complete.  Then the FDA needs time to evaluate the results and make a decision about whether the therapy can be marketed.

Q: What role, if any, did the National MS Society play in the development of ocrelizumab?
A: The Society did not play a specific role in the development of ocrelizumab. However, the Society has funded early studies that increased understanding of the role of B cells in the immune attack of MS, as well as an early clinical trial of rituximab, a therapy similar to ocrelizumab. The Society continues to fund researchers exploring the importance of B cells, in relapsing and progressive MS. The Society also provides leadership to the International Progressive MS Alliance, which is funding a study testing rituximab in progressive MS.

Rebif is a trademark of EMD Serono.