Interest in Ocrevus (ocrelizumab), the first FDA-approved treatment for both relapsing and primary progressive multiple sclerosis, is running high among patients and the organization representing them — as, arguably, are expectations of its use.
But how do physicians involved in MS care view the newcomer?
Lisak, who holds the Parker Webber chair in neurology and is also a professor of immunology and microbiology at Wayne State University School of Medicine, is widely published. A past editor in chief of the Journal of Neurological Sciences, he also served as board chair of the CMSM Foundation (FCMSC). He has devoted a large part of his career to MS, for which he received the CMSC Lifetime Achievement Award in 2011, among other honors.
Highly awaited new treatment
Lisak — one of the neurologists at Wayne State treating MS patients who participated in the Phase 3 Ocrevus trials — called it “certainly the most awaited approval for an MS treatment in a long time.” He had been hoping, he said, for the drug to be approved.
While he was blinded to treatment assignments during the study — as were all of the study staff — he acknowledged that its benefits to treated patients were evident once the study ended.
Ever since the first Phase 3 trial data were released in 2015, Lisak also said that his patients have been awaiting Ocrevus’ approval, bringing forward questions, hopes, and concerns in their discussions with him.
The interest among primary progressive (PPMS) patients, not surprisingly, has exceeded that of relapsing (RMS) patients, he said. Ocrevus does what no drug before it has succeeded in doing — slowing the relentless progression of the disease, to offer new hope to the thousands of people who got little help from medications approved for relapsing MS.
For those with relapsing forms of MS, likewise, “[t]here seems little question that ocrelizumab, marketed as Ocrevus, seems to be one of the most highly effective treatments … with reassuring and acceptable safety data to date.”
Although the treatment is given as an intravenous infusion, after the first administration two weeks apart, patients only need to put aside one day every six months for the infusions — a feature that Lisak believes adds to its perks.
But when Multiple Sclerosis News Today asked Lisak if he believes Ocrevus to be a “game changer” — a description used by many when its approval was announced, including the president of the National MS Society — he was more cautious. “I am not sure what one means by a ‘game changer,’” Lisak said.
“In primary progressive MS 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,” he said.
Its potential as a highly effective relapsing MS treatment is also clearly established.
“[But] if ‘game changing’ means that all patients with relapsing MS 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,” he added.
With one week to go before the drug is expected to hit the market, Lisak main concern circles around reimbursement and access issues.
“The big unknown is how insurance companies and other third party payers will respond when a patient is prescribed Ocrevus,” he said.
The U.S. Food and Drug Administration (FDA) approved Ocrevus for relapsing MS without any restrictions in terms of earlier treatment outcomes. In theory, this means that a patient can receive Ocrevus without having to prove that other treatments had failed.
But Lisak doubts that insurance companies and third-party payers will abide by this, stating that he sees tiering of other MS drugs that are approved without restrictions.
“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,” said Lisak, underscoring his disapproval of a situation in which insurers ultimately get to decide which treatment a patient receives.
The list price of Ocrevus does not particularly concern Lisak, who called its $65,000 annual price tag lower than that of other established treatments. “Unfortunately we do not know what each individual insurance company/third party payer is paying for any of the drugs,” Lisak said, adding that “the lack of transparency on the part of the payers and pharmaceutical companies” is of major concern.
But the issue of access is not new. In Lisak’s view, poor access to MS treatments — be it linked to costs, changing insurance coverage, or inadequate supply — is a recurrent issue. And, despite what many might think, it is not restricted to disease-modifying treatments.
Patients have equal difficulties obtaining access to symptomatic, physical, occupational, or speech therapy, and even medical equipment, according to the neurologist. “And I find it unacceptable and disgraceful,” Lisak said.
But access is not the only area of concern in Lisak’s view. As with any new treatment — particularly one that has major effects on the immune system and is used in a chronic disease like MS — there are side effects to look out for.
Infusion reactions, airway infections, and herpes were the most commonly reported side effects during the Phase 3 trials. Most of the time, Lisak noted, they were either mild or moderate, and infections were treatable. He also mentioned the finding of more cancer cases among patients receiving Ocrevus than in the respective control groups in the trials.
And he noted that side effects were similar in patients with relapsing and primary progressive disease, making them a bit more acceptable for progressive patients who lack other options.
While “hopes are high,” Lisak stressed that Ocrevus is, by no means, a cure for “either population of MS patients.”
“It is important to remind [progressive] patients that ocrelizumab did not stop progression for the treated patients as a group, it reduced progression by 24 percent compared to the placebo control group,” he said.
“We obviously need to see what the long-term effects are, as best we can in the absence of long-term controlled trials,” he said, adding that the identification of long-term safety concerns will be a key part of such observations.
Long-term experience with a treatment could unearth unexpected issues. “You cannot always predict based simply on current observations,” Lisak said.
Although the side effects are, in Lisak’s view, mostly acceptable, he is puzzled by a feature of the clinical trials’ data.
In relapsing patients, brain scans showed a nearly complete stop in the formation of new inflammatory brain lesions. And those with primary progressive disease had fewer lesions at the trial’s end than when it begun, in contrast to the ever-increasing lesion load in the placebo group.
The treatment’s clinical effects, measured in terms of flares (relapses) and disability progression, were also impressive, but they did not mirror the nearly complete extinction of new brain lesions in relapsing patients, or the reversal of lesions in primary progressive patients.
“We do not understand the reasons for this disconnect between the clinical and the imaging data, or the long-term implications of this finding,” Lisak said.
“While there is not always a perfect correlation between clinical outcomes and MRI [magnetic resonance imaging] measures, these are somewhat unusually disparate,” he added, underscoring that there is plenty more to be learned about what is going on in the body of a person with MS.
A full transcript of the interview with Dr. Robert Lisak can be found here.
CMSC 2017 conference awaited
CMSC’s Annual Meeting, set for May, will be the first major MS meeting since Ocrevus’ approval. June Halper, CMSC’s CEO and a key force behind the development of clinical practice guidelines for MS, acknowledge that Ocrevus data will most likely be discussed at the meeting. While she could not provide any details because the abstracts are not yet public, “we are expecting” ones from Genentech, the treatment’s developer, Halper said.
CMSC is also accepting late-breaking abstracts until May 1, making it possible that Genentech will submit additional analyses of the clinical trial data for this meeting.