Lisak, a professor of neurology and of immunology and microbiology at Wayne State University School of Medicine, is a former president of the CMSC and a widely recognized neurologist with expertise in MS.
Q: Ocrevus has been called a game-changing MS treatment. From your considerable experience treating and caring for MS patients, would you agree?
A: I am not sure what one means by a “game changer.” This is certainly one of the most highly anticipated approvals ever since the presentation of the results of the trials at the ECTRIMS meeting in Barcelona in 2015.
In primary progressive MS [PPMS], it certainly will have an immense impact, since there is currently no other approved therapy for any progressive form of MS. And trials of other treatments for PPMS have basically been negative. In relapsing-remitting MS [RRMS] — more appropriately, many of us think, better called relapsing forms of MS (RFMS) or relapsing MS (RMS), since it takes into account patients who are still having relapses superimposed on a secondary progressive course — there seems little question that ocrelizumab, marketed as Ocrevus, seems to be one of the most highly effective treatments for RRMS/RFMS with reassuring and acceptable safety data to date.
The ease of treatment with intravenous infusions twice per year, after the initial two doses two weeks apart, is certainly also very attractive.
If “game changing” means that all patients with RRMS/RFMS/RMS should be on this treatment even if they are doing very well on other disease-modifying agents, then I worry about the use of that term.
Q: Do you have any concerns about Ocrevus, perhaps in what you are professionally hearing or reading, or are you viewing the arrival of this therapy with expectation and hope?
A: I was certainly hoping to see approval, since [we need the] addition of another highly effective treatment for MS, and in particular an approved effective treatment for PPMS.
There are always areas of concern with any new therapy, particularly one that has major effects on the immune system and [that is] being used in a chronic disease like MS. The infusion reactions seem to be manageable, respiratory infections also of concern but treatable, a minimal increase in herpes infections, not disseminated and once again treatable, and finally potential for increase in malignancies. In the studies there were more cancers than in the interferon-beta 1a control group (in RMS studies) and placebo group (in a PPMS study).
Q: Do those concerns — or hopes — apply equally to relapsing MS patients and primary progressive MS patients?
A: The clinical effects on relapses were impressive, as was the effect on disability, but interestingly there was a more striking effect on reduction of lesions and other MRI measures. We do not understand the reasons for this disconnect between the clinical and the imaging data, or the long-term implications of this finding.
In the patients with PPMS, similar side effects were of concern, but the lack of any current alternatives might mitigate to some degree the concerns. And in PPMS it is important to remind patients that ocrelizumab did not stop progression for the treated patients as a group; it reduced progression by 24%, compared to the placebo control group. So while hopes are high, this treatment is not a cure for either population of MS patients.
Q: Given your clinical experience, would you expect a reduction in new brain lesions — of the magnitude seen in the trials — to result in a larger impact on relapses and disability progression?
A: While there is not always a perfect correlation between clinical outcomes and MRI measures, these are somewhat unusually disparate.
Q: Interest in Ocrevus, from all that we see and hear, is quite high among both neurologists and their patients. Do you agree?
I agree. As I said, [it’s] certainly the most awaited approval for an MS treatment in a long time.
Q: Are patients discussing Ocrevus with you? Is interest particularly strong among PPMS patients, or equal for both PPMS and RMS patients?
A: Patients have been discussing and asking about this treatment since the end of 2015, when the data was first presented. And in my experience [there is] more discussion and apparent interest in patients with PPMS, since they had no therapy or in some instances were taking treatments for RRMS/RFMS/RMS, already shown to be ineffective in studies, and getting worse.
Q: Compared with what you have experienced with earlier rollouts of MS treatments, when Ocrevus becomes available to U.S. patients — in about another week — do you foresee problems with access or supply? Or, in your opinion, are things well in place?
A: Only Genentech/Roche can answer that question. We have been told it would begin to be available early in April.
The big unknown is how insurance companies and other third-party payers will respond when a patient is prescribed ocrelizumab (Ocrevus). Will there be tiering, particularly for patients with RRMS/RFMS/RMS, which is not how the FDA approved this MS treatment or basically the other MS treatments; and yet we see this all of the time. Will they place restrictions on the use in RRMS/RFMS/RMS?
The decision on who should be treated with MS treatments, which ones at which times and in which sequence, should be the decision of the physician and the patient and nothing else.
Q: In your experience treating MS patients, is access to a particular and wanted treatment — because of costs, changing insurance coverage, adequate supply — a recurrent issue or problem?
A: Access to treatments in MS, and not just for disease-modifying therapies, but also for symptomatic therapy, physical/occupational/speech therapy, medical equipment, etc., is a recurrent problem. And I find it unacceptable and disgraceful.
Q: Do you treat or know of patients who have gone through the Ocrevus clinical trials? If so, have you seen the treatment’s benefits, or have these patients spoken of benefits, or problems, to you?
A: Our center was part of OPERA II (one of the RRMS trials [NCT01412333]) and ORATORIO (the PPMS trial [NCT01194570]). During the trial we were appropriately blinded as to which patients were receiving ocrelizumab or interferon-beta 1a in the OPERA II trial, or placebo on the ORATORIO trial, so there would be no way to know about benefits or problems related to ocrelizumab. However, since the trials have ended, it is clear that patients seem to have benefited from treatment.
Q: Does Ocrevus’ list price — $65,000 a year — concern you? Or is it reasonable in comparison with other treatments, and given what you know of insurance and other support programs in place (by Genentech and others) for patients who are underinsured or uninsured?
A: Actually, the announced list price, while expensive, is actually lower than many established therapies. And unfortunately we do not know what each individual insurance company/third-party payer is paying for any of the drugs. One assumes there is some negotiating, unlike CMS who does not negotiate, although other federal agencies certainly do. The lack of transparency on the part of the payers and the pharmaceutical companies is of major concern. I do not know the details of any plans by Genentech for support programs. Many of the other companies have plans in place to help patients who fulfill certain and variable criteria.
Q: Are there other issues, topics, or concerns about Ocrevus, based on what you know of it, that you would like to address?
A: We obviously need to see what the long-term effects are, as best we can in the absence of long-term controlled trials, and to see if there are any safety concerns, either already identified or unexpected. The latter is the Black Swan effect. You cannot always predict based simply on current observations.