MSAA’s Dr. Jack Burks Responds to Readers’ Questions About Ocrevus and Its Use

MSAA’s Dr. Jack Burks Responds to Readers’ Questions About Ocrevus and Its Use

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.

“There is tremendous interest [in Ocrevus] from MS patients with primary-progressive MS (PPMS) as well as relapsing forms of MS (RMS),” Burks said.

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.

Practicalities

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.

Similarity controversies

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.

18 comments

    • Grace Frank says:

      Hello Mark

      Apparently, Ocrevus is still under a review of some sort by Veterans Affairs, but an online VA post (a PDF) includes this almost final graph:

      Availability in VA. Ocrelizumab will be available under the non-formulary request process at
      the facility level. This process will be implemented until the National Review is completed.
      Ocrelizumab procurement does not require a Specialty Pharmacy process — it will be available
      through the McKesson Plasma and Biologics division. The pricing will be open market until the
      FSS paperwork has been implemented.

      So, if we understand this language correctly, your individual VA facility should be able to help you acquire access to Ocrevus, even while the “National Review” (apparently a CFU, or criteria for use) is ongoing.

      Here is the link to the VA PDF that I cite above: https://www.va.gov/MS/Professionals/medications/OcrelizumabConsiderationsDecisionFinal2.pdf

      Hope this is of help to you and other veterans.

  1. Kenny says:

    “12% of the female populated has been diagnosed with breast
    cancer.” This quote by Burks is Erroneous if you factor in age groups!
    Women under age 35 are not in that 12% number

  2. charles says:

    i am planning to switch to ocrevus, and i expect it to quickly become the new standard against which new therapies are compared. at least i hope that it will.

  3. Anonymous says:

    You stated that breast cancer rates were in line with what is seen in the general population. Why did breast cancer only show up in patients treated with Ocrevus?

    • Magdalena Kegel says:

      At this point, it is possible that the increase is just a chance finding. But researchers do not know if the increase is real and tied to Ocrevus, or not. They are currently looking at this, and other issues, in long-term safety studies of the drug. So far, a further increase in cancer rates have not been reported.

  4. Kenny says:

    This message is directed to Magalina Kegel. You are a writer with a PhD and you call the information about breast “chance findings.” That is disgraceful!
    If you are going to inform patients about a drug therapy please do not
    indulge in “fake reporting.”
    Saying that 12% number for breast cancer rates is erroneous when it is broken down into “age” groups.

    • Magdalena Kegel says:

      Dear Kenny

      As a writer for Multiple Sclerosis News Today, I do not forward my own opinion in my articles, nor do I report data from unverified sources. Our reporting is strictly based on published scientific findings, or on interviews with researchers or physicians who are experts in their field, and we are obligated to report their statements as they give them in response to our questions. I note that all articles published on MS News Today are scrutinized by editors and fact checkers against the original documents or interviews.
      Genentech has repeatedly said that, at this time, there is no data supporting any claim that Ocrevus causes breast cancer (see, for instance, interview with Dr. Peter Chin, Genentech’s Group Medical Director, Neuroscience).

      The company’s statements indicate that if there is no causal link between the treatment and the higher rates of breast cancer — and cancer in general — so that this may be a chance finding, as I expressed in an earlier comment to this article. In other words, my statement and my reporting are based on publicly available data released by Genentech, which holds all data to these trials, and on the fact of the treatment’s FDA approval, an agency that is obligated to investigate data prior to approval.

      Dr. Burks cited official statistics for breast cancer, which state that 12% of women will develop breast cancer over their lifetime. As several readers have pointed out, rates are significantly lower in younger women. They do, however, rise dramatically with age (please see this article for reference).

      In the trials, breast cancer occurred in 0.24% of relapsing Ocrevus-treated patients, and 0.8% of PPMS patients of Ocrevus. Rates of all cancers were 0.5% and 2.3% in the relapsing and PPMS groups, respectively. These figures are within the norm, as Dr. Burks and, before him, Dr. Chin pointed out.

      We do not have specifics, such as age, of the women affected by breast cancer in the trials. Even if we had such data, it is not up to me — as a reporter — to speculate on how age relates to the cancer findings in the Ocrevus trials. The most I could do is to question such findings relating to specifics as age, were data available, which they are not.

      When Genentech, or any research company or group, makes public new data regarding cancer rates in Ocrevus-treated patients, or its interpretation of such data, we will make sure to share that information with patients. But we cannot neither create such data, nor can we fail to report the data available to us as presented. To do so is to fail to inform you of information you need to judge — and to question with your doctors — available data as you think best as a patient.

  5. Anonymous says:

    Once I start treatment with Ocrevus is there any way to reverse the drug or clean it from my system should I develop a serious sustained side effect like an infection?

    • Magdalena Kegel says:

      Hello,
      The drug will be cleared from your body, but since Ocrevus is only given two times a year it does so at a slow rate. The half-life of the drug — at which the initial levels of the drug have been halved — is 33 weeks.

  6. Rimp says:

    I noted that no one over 50 was studied in the trial.My friend is 65 with a new diagnosis of PPMS.Do you know how Medicare is paying for Ocrevus?

    • Magdalena Kegel says:

      Hi Paula,

      In the OPERA trials, there was a total of 6 cancers among 1651 patients. Four among Ocrevus-treated patients and two in the interferon group. In ORATORIO, there was a total of 13 cancers, 11 among 486 patients on Ocrevus and 2 among 239 patients who received placebo.

  7. Syeda says:

    Iam ms patient from last 2013 oct and on tysabri now Iam 37 now my neurologist has suggested me this drug now I’m reading chances of breast cancer can u plz mention age group who can get breast cancer and is that safe
    As ms patient we expect this will be a miracle drug but I’m really scared as I’m doing fine on tysabri will I still be able to walk on this new drug

    • Magdalena Kegel says:

      Dear Syeda,
      Patients in the OPERA trials were on average 37 years old. In the ORATORIO study, they were about 45. Researchers still do not know if the risk of breast cancer is really tied to Ocrevus. All MS drugs have their risks, and so far, no drug cures MS. It is only you, together with your neurologist, who can decide if Ocrevus is the right treatment for you.

  8. Sierra says:

    I’m curious what cancer rates are in the general population when you measure it in a given snapshot in time (like the trial i.e. 2 yrs or 3 yrs or whatever)? Are the rates quoted in the commentary lifetime rates or comparable snapshots in time to the trial length?

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