#CMSC17 – Ocrevus, Progressive MS and Other Research Highlights: An Interview with CMSC’s Robert Lisak

The recent annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) brought researchers and healthcare professionals to New Orleans to discuss advances — and obstacles to advances — in multiple sclerosis (MS) research.

Clinical trials, preclinical studies, basic research, and health interventions were among the May meeting’s focus.

Multiple Sclerosis News Today reported on a number of key presentations. But to get a feeling for those that mattered most to someone closely involved with both MS patients and research, we turned to Dr. Robert Lisak — a neurologist and past president of CMSC.

Lisak shared his thoughts on presentations he found important and encouraging. And he spoke of he would like to see addressed at future meetings.

As at any MS conference, plenty of attention was given to clinical trials of potential new therapies, as well as trials gathering more information about already approved drugs.

When asked about — in his view — the most promising of these studies, Lisak specifically mentioned those looking at three drugs: the recently approved Ocrevus (ocrelizumab), the investigational drug siponimod, and trials on high-dose biotin (like MD1003).

Ocrevus updates

“Obviously, the approval of ocrelizumab for PPMS [primary progressive MS] has gotten a lot of attention as it is the only approved treatment for PPMS at this time,” Lisak said.

The attention, he indicated, is, at least in part linked to the novelty of the findings.

“Every time there is a newly approved treatment, or even a study supporting a positive effect of a new treatment, or even a repurposing of a treatment originally used for another disease, it increases interest and hope.”

But in the case of Ocrevus, professional interest goes beyond its novelty.

“The approval for progressive disease with an agent that is anti-inflammatory raises the possibility that there is more inflammation involved in progressive phases of the MS than is generally acknowledged,”he said, emphasizing how little is really known about disease processes in progressive MS.

According to Lisak, the meeting updates on Ocrevus were reassuring. He particularly mentioned studies of continued effectiveness and safety.

In extension trials of relapsing MS patients, Ocrevus was seen to reduce relapses even further than in the original Phase 3 studies. And analyses of both primary progressive and relapsing patients showed that the safety profile was consistent with that seen in the original clinical trials.

When asked about the imbalance in cancer cases seen in the Ocrevus Phase 3 trials — a topic that concerns many — Lisak’s answer captured that imbalance rather well.

“Certainly one always worries about both opportunistic infections and increase in cancers with any immunosuppressive therapy,” he said.  “What is somewhat strange about the data for cancers, particularly breast cancer, was the lack of any [breast cancer] cases in the placebo arm (PPMS study) or interferon beta treated arm (RRMS studies) in the publications [of the clinical trial data].” In total, four Ocrevus-treated PPMS patients, and two RRMS study patients,  developed breast cancer.

With studies of this size — Lisak said — it was strange to not have a single breast cancer case in the placebo and Rebif (interferon beta-1a) control groups. This illustrates that the imbalance in breast cancer cases is, in part, caused by the unusual lack of cases in the trials’ control groups — a point Genentech refers to when noting that cancer cases within treated patients were “within epidemiological [general population] reports.”

“I doubt,” he said, “anyone thinks that placebo infusions or interferon beta prevents breast cancer.”

Spotlight on progressive disease

A few investigative treatments also caught Lisak’s attention.

“There was important discussions about siponimod for SPMS [secondary progressive MS] and studies of biotin for SPMS/PPMS that are ongoing.”

A Phase 3 trial, presented at the recent American Academy of Neurology’s annual meeting, showed that siponimod reduced the risk of disability progression by 21 percent over three months. And a Phase 3 clinical trial of MedDay’s high-dose biotin MD1003 was recently launched to confirm earlier positive findings in progressive MS.

Meanwhile, it is becoming clearer that stem cell transplant approaches are not benefitting progressing patients.

“I think the stem cell therapy discussions have made it obvious that this is not a likely successful approach to slowly progressing patients in more ‘purely’ degenerative stages of the disease,” said Lisak.

In addition to specific treatments, advances in how researchers measure disease activity and progression are important contributions in trying to treat progressive disease stages, he noted. Such efforts also encourage the development of protective and reparative treatments, Lisak added.

But progressive MS remains an enigma to researchers. To advance their knowledge, Lisak said that presentations, going into details of trials of progressive MS treatments — including negative ones — would be valuable.

“It would help us in understanding how to do studies in progressive disease, as well as give us additional insights into mechanisms of progression, which are incompletely understood and often looked at in a very simplistic manner,” Lisak said.

Symptomatic treatment

While the goal of MS treatments is to prevent relapses in relapsing patients and disability progression in both relapsing and progressive ones, drugs that address specific MS symptoms might make life easier for patients living with the disease.

When asked about studies of potential new symptomatic treatments, Lisak did not mention any one specific therapy. Rather, he underscored that a “continued emphasis [on] multidisciplinary treatment is important.”

But he also mentioned that studies of sexuality and the treatment of related problems is starting to “see the attention it deserves.”

Mental health in MS is another field that Lisak said needs more attention.

“I think there needs to be more emphasis on evaluation, but even more than that, more research on treatment and treatment effect,” he said.

Future studies using modern imaging techniques to link treatment to measurable effects on the brain are also needed, he said.

Clinical trials and beyond

With the increasing amount of disease-modifying treatments on the market, Lisak found it encouraging that greater emphasis is being placed on studies that attempt to define best approaches for switching between therapies. And induction versus escalation approaches in MS treatment is a growing research focus, which — in Lisak’s opinion — is a good thing.

But to understand MS — as with every disease — clinical trials are not enough. The efforts of researchers exploring cellular and molecular mechanisms are invaluable, and guide the development of new treatments.

We asked Lisak if he thought that MS research is going in any particular direction.

“I think additional work on microbiome, microRNA, further investigations into newer role of T cells, B cells and microglia are important,” said Lisak. “I also see trying to approach stem cell therapy in a logical and critical manner a big plus.”

The CMSC meeting and its highlights act as a reminder that — behind the sporadic reports of positive treatment effects of a new MS therapy — there is a huge congregation of scientists and healthcare professionals that spend their days attempting to make life better for the thousands of MS patients out there. And they are slowly, but steadily, succeeding.