Recently approved, Ocrevus (ocrelizumab) should now be available nationwide for patients prescribed the therapy. But as with any new treatment, concerns about safety and practical issues are on many patients’ minds.
Multiple Sclerosis News Today asked Dr. Jack Burks — a neurologist and researcher who serves as chief medical consultant to the Multiple Sclerosis Association of America (MSAA) — to comment on various concerns voiced by its readers, most of whom are MS patients.
With an imposing biography, Burks is in an excellent position to discuss MS-related matters. He has worked for more than 40 years with MS — founding MS centers and having written textbooks on the disease.
The Genentech-developed prescription medicine — which comes in the form of an infusion — is given twice a year. One exception is the first dose, split into two doses given two weeks apart.
“Dividing the initial dose into two half-doses reduces the risk of infusion reactions. Six months following the first two-part infusion, the full 600 mg dose is given in one infusion and this dosing continues every six months thereafter,” Burks said. Then, addressing one concern, he added that no one need be concerned about bladder issues during the infusion.
As the full dose should be given over at least 3.5 hours, some patients have wondered whether bladder problems might prevent them taking on the treatment.
“Infusion centers are well equipped to help patients with bladder-control issues, including those in wheelchairs,” Burks said.
Pros and cons
The main concern of many patients, however, is safety. Or, put in other words, if the risk of side effects justifies the treatment’s intended benefits.
When it comes to benefits, Burks puts his trust in the clinical trial data. “The effectiveness data is substantial and statistically significant in relapsing forms of MS — which includes relapsing-remitting MS and secondary-progressive MS with relapses — as well as for primary-progressive,” he said.
While the trial in PPMS patients showed a 24 percent reduction in the risk of disability progression, Burks pointed out that other, more sensitive measures, might reveal more about the drug’s effectivity in PPMS patients.
“Risk of disability progression is not likely to be as dramatic as magnetic resonance imaging (MRI) and other outcomes, since many untreated patients may not get dramatically worse over a two-year period,” Burks said, adding that significant differences in disability were seen between Ocrevus- and placebo-treated patients, even at two years.
“More sensitive outcome results were more dramatic,” he said, speaking about how MRI scans revealed that the treated group had a decrease in brain lesion volume during the trial, while those on placebo had a steady increase.
Other data, including a walking test, also demonstrated that Ocrevus made a difference.
In a similar way, he referred to improvements seen in relapsing patients as “dramatic.” Ocrevus reduced relapse rates by 46% and 41%, decreased the risk of disability progression by 47% and 37%, inflammatory MRI lesions by 94% and 95%, and new and enlarging MRI lesions by 77% and 83%, he noted.
While Genentech has not released specific data for secondary-progressive relapsing patients in the trials, Burks underscored that efficacy in these patients was consistent with that of relapsing-remitting patients. Safety was similar in all the trials.
“Ocrevus is considered an effective treatment for both RMS and relapsing SPMS,” Burks said. Whether secondary-progressive patients without relapses would benefit from the treatment has not been studied.
As with every treatment, benefits come with the risk of side effects. And while Burks thinks that “the two years of data is encouraging” in terms of safety, there is no guarantee that new side effects will not appear as more people are treated for longer periods.
“As with any clinical trial, we must be vigilant to investigate side effects and adverse events over time,” Burks said, adding that he found it reassuring that no negative effects on major organs, such as kidneys, liver, thyroid, or heart, were reported during the trials.
“The FDA warnings include active hepatitis B and severe infusion restrictions. However, the overall serious side effects were not different than the control groups, except for infusion reaction. Less than 1 percent of Ocrevus-treated patients had severe infusion reactions,” he said.
Many have also noticed that the clinical trials showed more people developing cancer — particularly breast cancer — in the Ocrevus, compared to control, groups. While continuing to investigate this finding, Genentech has said that the trial’s cancer rates were within the norm for the population — a statement Burks agrees with.
“More breast cancer was detected in treated patients, but the numbers do not exceed the average population numbers for this female age group. Breast cancer is rather common in the general population of women. In fact, 12 percent of the normal female population has been diagnosed with breast cancer,” Burks said.
Since the completion of the three Phase 3 Ocrevus trials, no new increase in cancer risk has been reported. “Nonetheless, we cannot predict the future risk, so the FDA recommends adherence to the standard breast cancer screening protocols,” he said.
One safety aspect still to be determined is the risk of multifocal leukoencephalopathy (PML) — a life-threatening viral brain infection linked to other MS treatments. For instance, some patients using Tysabri (natalizumab), Gilenya (fingolimod), and Tecfidera (dimethyl fumarate) have developed PML. And Rituxan (rituximab) — similar, but not identical to Ocrevus — has been linked to the condition.
So far, no one treated with Ocrevus has developed PML, but Burks acknowledges that fact is not a guarantee. He encourages patients to speak with their neurologist about new findings of side effects — or benefits, for that matter.
“RMS patients still have a choice of several MS therapies, each with their own set of benefits and side effects. Every patient and doctor must discuss the potential long-term risks as well as benefits. This shared, decision-making process will increase adherence to the treatment and increase vigilance for future risk factors,” he said.
For PPMS patients, Ocrevus is the only approved treatment available.
Neurologists should also advise patients on managing a transition to Ocrevus from another treatment, Burks said, since a switch in treatments was not evaluated in the trials.
Studies assessing the long-term safety of Ocrevus are also underway, he pointed out.
Weighing potential benefits and harms is only part of the considerations patients give a treatment. For the majority who cannot afford to pay for Ocrevus — $65,000 per year — out of pocket, cost is also a large issue. We asked Burks if he thought that price might be a barrier to Ocrevus access.
“This depends on people’s insurance coverage and support received through patient assistance programs,” he said, adding that the cost of Ocrevus is similar to many other MS treatments.
“Fortunately, it is not priced exorbitantly high just because this is the only treatment available to the PPMS patient population,” he said.
Burks thinks most health insurance plans will likely include some coverage for Ocrevus. He also mentioned that, for patients lacking sufficient coverage or with no insurance at all, Genentech has a patient-assistance program and the MSAA maintains a list of pharmaceutical patient-assistance programs on its website.
Since its approval, many have commented that Ocrevus is similar to an earlier Genentech drug, Rituxan — an antibody medication also targeting B-cells of the CD20 type. With a researcher’s attention to detail, Burks gave us his view on the two therapies.
“Every monoclonal antibody therapy is different,” he said. “There is no MAB [monoclonal antibody] for MS in a ‘generic’ form. Rituxan is derived from mouse tissue and is different than human-derived Ocrevus.”
He also pointed out that Rituxan — sometimes used off-label for MS treatment — has not been adequately studied in MS, and is, therefore, not approved for the condition.
“Since Ocrevus is a humanized anti-CD20 monoclonal antibody, it may be better tolerated with fewer side effects and less infusion reactions,” Burks said, and underscored the importance of looking at data when discussing MS treatments.
“While we cannot predict the future, the current data supports Ocrevus for MS,” he concluded.