Ocrelizumab Approval to Shift Multiple Sclerosis Treatment Landscape

Patients, advocates, and researchers alike are celebrating after the FDA approval of the long-awaited multiple sclerosis (MS) drug ocrelizumab (Ocrevus, La Roche). To date, ocrelizumab is the first and only treatment approved for patients with primary progressive MS.

Ocrelizumab is a humanized monoclonal antibody designed to target CD20-positive B cells for the treatment of both relapsing and primary progressive MS. Review of the Biologics License Application of ocrelizumab took place today, after being delayed by the FDA in December 2016.

Dr Michael Racke, professor of neurology and neuroscience at Ohio State University Wexner Medical Center, known for his research in immunology and MS, spoke with Specialty Pharmacy Times regarding the importance of ocrelizumab and how it will change the MS landscape.

SPT: What role did the Ohio State University Wexner Medical Center play in the upcoming approval for ocrelizumab?

Dr Racke: We were a site for both OPERA and ORATORIO, clinical trials analyzing ocrelizumab. For OPERA, there were 2 trials: OPERA 1 and OPERA 2, which looked at ocrelizumab as compared to interferon beta-1a, so it was a head-to-head trial, which was a little bit different. A lot of times MS medications first are against placebo, but this one was against a very good MS medication and ocrelizumab did very well. There are no approved drugs for primary progressive MS, and ORATORIO was the first trial to show a benefit in primary progressive MS. So that’s the reason the FDA gave it breakthrough drug status, and we were also a site there.

I think from the Ohio State prospective, we’ve been very much involved in kind of the forerunner of ocrelizumab with a drug called rituximab. We did a clinical trial with rituximab in primary progressive MS, and it did not work. But when we analyzed the data, the patients were under the age of 51 or who had active disease and appeared the drug was beneficial for those patients. Genentech was involved in that initial study, and when the ocrelizumab study came out, they went with a younger patient population. The average age of the patients in ORATORIO was 5 years younger than our national rituximab study but beneficial. If you look at it as a whole—–at both the OPERA studies and the ORATORIO study––the major effect of this monoclonal antibody really is that it reduces inflammation dramatically in MS.

SPT: How will ocrelizumab change the treatment landscape for patients with MS, particularly these forms of the disease?

Dr Racke: It has a big effect on relapsing patients. If you look at what’s available in the monoclonal antibodies in terms of safety, I would say that the safety profile—–at least so far––looks much better than natalizumab and alemtuzumab. Natalizumab was the drug that after it had its initial FDA approval was pulled off the market for a while because of cases of progressive multifocal leukoencephalopathy. There continues to be a trickle of patients who are diagnosed with that disorder, [but] there are no cases reported of ocrelizumab having that effect.

Alemtuzumab also has a very high efficacy profile but it also has baggage. Within 5 years, approximately 50% of patients get another autoimmune disease despite [alemtuzumab] working pretty well to treat their MS. I think that from the patient’s perspective the opportunity to get a highly-efficacious monoclonal antibody that just has a lot less [issues] of the other monoclonal antibodies, that’s going to make a big difference for the patients.

SPT: What are the biggest advantages ocrelizumab has over other MS drugs on the market today?

Dr Racke: When you look at the initial MS drugs like interferon, copaxone, they basically showed a 30% reduction in relapse rates compared with the placebo. This basically shows almost a 50% reduction in relapse rates compared with high-dose interferon. One of the major drivers of why it got approved was it had a 90% reduction in new MRI lesions. When you compare ocrelizumab to interferon beta-1a, you see about another 90% or greater than 90% reduction in new MRI lesions. You have the ability to inhibit new lesions for this drug way better than anything that we’ve seen before.

A major outcome measure, and this is a secondary outcome, is something called ‘no evidence of disease activity,’ or NEDA. When you look at a drug like interferon beta-1a, which is what ocrelizumab was compared to in this trial, it’s NEDA for interferon beta-1a with about 25% maybe a smidge higher than that, it was 48% for ocrelizumab. That means that almost half of the patients that enrolled in the trial had no new lesions, relapses, [and] no progression of disability. That’s really the goal that we want to eventually have for these patients, that they don’t really experience any new disease activity.

SPT: There has been constant conflict over the cost of drugs. Do you know what the cost of ocrelizumab will be set at if approved?

Dr Racke: I have not heard anything about that, but I can tell you that that’s obviously a big issue in terms of what’s going on with patients with MS. When beta interferon was approved back in the mid-90s it was $10,000 dollars. I believe the last number I saw for beta interferon was something like $90,000 a year, [and] alemtuzumab is $100,000. So, I suspect it’s going to be somewhere in that range. But I think this is a big issue in terms of MS.

I was on capitol hill last week advocating with the MS society for more transparency in drug pricing, and one of the things the MS society would like to see is that companies have to justify why they are increasing a price over 10% in a year or over 25% in 3 years. Because eventually you’re going to price patients out of having access to these drugs. Some people are paying as much as $1000 out-of-pocket, and that really prices a lot of patients out of the ability to have access to these medications.

SPT: What do you want people to know?

Dr Racke: We have about 70 patients on ocrelizumab right now in various trials. But we have over 100 patients on rituximab, which was forerunner drug that is FDA approved for lymphoma, and I’m interested to see what will happen.

Now there are several monoclonal antibodies that are also directed against this, and I guess one of the questions that’s going to be interesting is are we going to continue to see increases in prices? With the debate of health care costs, 1 of the arguments has been that if you had competition in insurance that that would make the prices go down. But clearly going from one MS medication to 15 MS medications, we haven’t achieved any decrease in price. It seems like in pharma it’s quite a bit different than how you would typically think of the law of supply and demand of competition and how market forces effect of the price.