Ocrevus (ocrelizumab), now approved for both relapsing and primary progressive multiple sclerosis (MS), is expected to become available in the coming week. While patients and neurologists are waiting, Multiple Sclerosis News Today spoke to Genentech about the treatment’s approval, future research plans, and what patients can expect in terms of access.

Dr. Hideki Garren — Genentech’s Group Medical Director of Ocrelizumab — has spent the larger part of his career, nearly 25 years, searching for a new treatment for MS. “It has been a long journey for Ocrevus and an even longer one for MS researchers like myself,” Garren told Multiple Sclerosis News Today.

But as with many other scientists, the path that would lead to Ocrevus was not obvious in the early days of his career — spanning both academic and pharmaceutical industry positions.

“Like nearly all other researchers, I have been focused on broadly immunomodulatory treatments or T-cell directed treatments,” Garren said. “What’s new and exciting about Ocrevus is that it is directed to only one component of the immune system, the B-cell, which should provide efficacy and safety advantages.”

Expected approval

Much happened since those early days, and today, researchers seem convinced that a treatment approach involving B-cells is the right way forward.

With the Phase 3 clinical trial data at hand, Garren was confident that the U.S. Food and Drug Administration would approve the treatment as Genentech intended — as the FDA indeed did — without any surprising tweaks to the drug’s label.

“We’ve discussed the Ocrevus registration with health authorities over the past several years and were confident the Ocrevus Phase 3 data supported the registration strategy,” said Garren, adding that Genentech had ongoing discussions with the FDA since first submitting the Biologics License Application for Ocrevus.

According to the label granted by the FDA, Ocrevus can be prescribed for a broad spectrum of MS patients — including those with primary progressive MS. As such, it is the first and only approved medicine for this patient group.

The two Phase 3 OPERA trials (NCT01247324 and NCT01412333) on relapsing MS also included patients that had progressed into secondary progressive (SP) disease, but who still experienced relapses. While Genentech’s Dr. Peter Chin earlier said that subgroup analyses, including those of relapsing SPMS patients, is on the agenda, the company has, so far, not released further information.

Garren simply confirmed that relapsing SPMS patients were among the Ocrevus-treated patients in the OPERA trials.

A move to reduce new drug prices

As at the launch of every new MS treatment, cost is a heavily discussed topics among patients. Garren confirmed that Ocrevus is priced at $65,000 per year. He again underscored that this is about 25 percent lower than Rebif (interferon beta 1-a) — a commonly used first-line option for relapsing MS, and the drug to which Ocrevus was compared in the OPERA trials.

To further underscore Genentech’s commitment to steering drug prices onto a more reasonable course, Garren added that Ocrevus’ price tag is about 20 percent lower than the average U.S. price of all approved MS drugs.

“We are committed to helping those who can benefit gain access to our medicine, which includes fair, reasonable pricing at launch, and over the lifecycle of Ocrevus,” Garren said. “We believe that treatment decisions should be made by the patient and his or her neurologist,” he added, echoing the opinion expressed by Dr. Robert Lisak, past president of the Consortium of Multiple Sclerosis Centers (CMSC), in a recent interview.

MS News Today had earlier approached the National MS Society on this issue, and its response underscored a belief that Genentech’s move may well impact the pricing landscape of MS treatments.

“The National MS Society applauds Genentech for their leadership in setting the wholesale acquisition cost (or list price) of Ocrevus at $65,000 per year,” Cyndi Zagieboylo, the society’s president and CEO, said in her response.

“The continually escalating prices of MS disease-modifying therapies are creating barriers to people with MS getting these life-changing medications,” she added. “Through its action on Ocrevus, Genentech is changing industry dynamics so that more people can access the life-changing treatments they need to live their best lives. We encourage other companies to follow suit, creating a drug pricing trend that keeps patients first.”

Garren also seems confident that Genentech will be able to honor its commitment to provide access to Ocrevus — within the two weeks announced by the company — despite a likely high demand.

“As part of the approval process, the FDA reviews the manufacturing process is adequate to meet patient demand,” Garren said, adding that the FDA approved Ocrevus and its manufacturing processes.

“As the world’s leader in the manufacture of monoclonal antibody medicines, Genentech implements all possible steps to ensure the adequate and rapid delivery of these important medicines to patients,” Garren added, indicating that access will not be hampered by delivery issues.

He underscored that bringing Ocrevus to patients with MS is the first step in Genentech’s commitment to patients.

A story to be continued

Ocrevus is now about to be rolled out on a large-scale. As with other new medicines, a launch is really only the beginning of a drug’s story. Garren pointed out that Genentech continues to study Ocrevus in several ongoing clinical trials.

Such studies include long-term extensions of the initial Phase 3 clinical trials. Participants in these studies have been taking Ocrevus for longer than any patients, and will provide important information on long-term efficacy and safety aspects.

But the company is also focusing its efforts on other aspects of the treatment. Two trials (NCT02861014 and NCT02637856) will study Ocrevus in patients who failed to respond to other disease-modifying treatments. Both are now recruiting up to 600 patients; NCT02861014 is enrolling at sites across Europe, and  NCT02637856 at sites across the U.S. and Canada.

Another study (NCT02688985), also recruiting, will focus on the drug’s mechanisms — attempting to understand more as to how Ocrevus prevents relapses and disease progression in both relapsing and primary progressive MS. Early stage relapsing patients are the focus of a fourth trial (NCT03085810) enrolling patients in the U.S, Canada, Europe and elsewhere.

A fifth new trial, sponsored by the University of Colorado, is one that many patients are likely to keep their eyes on. This study (NCT02980042) will examine how patients tolerate a switch from rituximab — another B-cell depleting treatment that is used off-label for MS — to Ocrevus.

The trial, which is not yet open for enrollment, will also directly compare RMS patients being treated with one or the other therapy.

This study may potentially answer a question raised by patients and others — are there particular differences in the effectivity and safety of rituximab and ocrelizumab, two compounds targeting CD20 B-cells in MS patients?

Ocrevus is now moving into its next chapter — that of wide, and likely long term, use beyond a clinical trial. What comes from such use, and continued research, may well determine how well Ocrevus will serve as a potential game changer, an expression Zagieboylo used in speaking of her and the society’s hopes for this treatment.

“As the largest private funder of MS research in the world, the National MS Society hopes this is just the beginning of the development of the next generation of treatments for MS,” she said, underscoring the group’s work toward its goal of “ending MS forever.”