Using Daclizumab (Zinbryta), Ocrelizumab (Ocrevus) to Treat MS

With the arrival of two new medications, the treatment of multiple sclerosis has reached a new frontier.

“We are down now to relapse rates of 1 every 5 years or better,” said Bruce A. Cohen, M.D., during his lecture at the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting. “Our problem is now no longer whether we can treat relapsing-remitting MS (RRMS), but rather, how do we use these agents?”

Cohen, who is a professor of neurology at the Feinberg School of Medicine at Northwestern University, provided physicians with an overview of the two newest MS drugs — daclizumab (Zinbryta) and ocrelizumab (Ocrevus) – as well as more established therapies for treating the disease during his lecture titled, “Personalizing the Personalizing the Management of Multiple Sclerosis: A 3 Dimensional View of Current and Emerging Therapies,” on Wednesday, May 24.

The goals of any MS therapies should be to limit disease activity and prevent relapse and progression, Cohen said. These factors need to be balanced with limiting treatment-related adverse effects. Physicians also need to address patient lifestyle choices — such as smoking – as well.

Cohen advised physicians that treatment itself should be targeted toward relieving symptoms, shortening relapses, and reducing frequency of relapses. Therapies should be initiated as soon as possible, before disability begins, Cohen said, adding that a multi-disciplinary approach to care best serves patients.

The newest drug available for MS treatment, ocrelizumab (Ocrevus) became available to physicians in March 2017. Ocrelizumab, Cohen explained, “depletes pre-B cells, mature B cells, memory B cells through antibody-dependent cell-mediated phagocytosis, antibody-dependent cell mediated cytotoxicity, complement-dependent cytotoxicity, and introduction of apoptosis.” It does this without damaging lymphoid stem cells and plasma cells.

Researchers put ocrelizumab through 3 Phase 3 trials, including two which occurred in parallel. The parallel trials determined that ocrelizumab was highly effective compared to interferon beta-1a SC, with low annualized relapse rates, in treating RRMS. MRI outcomes also showed benefits consistent with reduction of inflammatory lesions.

“Perhaps one of the more exiting events this year was the third trial of ocrelizumab,” Cohen said, which looked at the drug’s efficacy against primary progressive MS (PPMS) compared to a placebo.

At 12 weeks, ocrelizumab kept disability progression to 32.9% vs. 39.3% in the placebo group. After 24 weeks, the figures stood at 29.6% vs. 35.7%.

“This has become the first approved drug for treatment of individuals with non-relapsing primary-progressive multiple sclerosis,” Cohen said.

From a safety standpoint, infusion reactions occurred in 34-40% of patients during the trials, Cohen said. These reactions were “most frequent and severe with early infusions but could occur at any infusion.” Infection rates were similar in the ocrelizumab and interferon beta-1a SC groups.

The other newer MS treatment option for physicians is daclizumab (Zinbryta). Daclizumab, Cohen explained, is a monoclonal antibody to CD25 that decreases IL2 signaling via high-affinity IL2 receptors, favoring signaling at intermediate affinity IL2 receptors. This causes an expansion of CD56 bright NK cells and enhances their immune regulatory functions.

Researchers put daclizumab through two trials. The first compared a 150 mg SC Q4W dose versus a placebo for 52 weeks. The second compared the same dose against and interferon beta-1a for 96 weeks. There was a 54% decrease in the relapse rate in the first trial, and a 45% decrease in the second trial.

Daclizumab, Cohen said, does have some safety concerns and comes with a hepatic injury black box warning. The drug requires hepatic enzyme testing prior to every monthly injection for 6 months following discontinuation, as well as screening for TB, HBV, and HCV prior to initiation. Daclizumab, Cohen said, shouldn’t be administered to patients with serious infections, and patients being treated with the drug shouldn’t receive live-virus vaccinations during the first 4 months. Researchers also noted increased frequency of depression in daclizumab groups during the trials.