Addressing Limitations in the Management of MS

Robert J. Fox, MD: In almost all patients, we have been able to take their relapsing MS [multiple sclerosis] and bring it under full control—stopping new relapses, stopping new or enlarging lesions on MRI [magnetic resonance imaging].

We don't always do it with the first or the second therapy, but in almost all patients, by the time we get to the third or fourth therapy, we have found a therapy that is going to stop their relapses and stop their new lesions on MRI. Through that we have converted relapsing MS in almost all patients to a fully manageable and controllable disease.

In contrast, with progressive MS, or that gradual, little by little decline in function—walking problems, bladder problems, coordination problems, cognition—we really have made very little inroad into slowing the progression.

When we can catch patients early in the progressive course, we do have therapies that can have a benefit. But later in the disease course, we really aren't able to stop that gradual, little by little decline. And so, treatment of progressive MS represents a huge unmet need.

Fred D. Lublin, MD: The lines of therapy are now getting blurred, in terms of first line, second line, highly effective, escalation. Those are all terms that are thrown around, but they actually have very little meaning. One has a long conversation with the patient, and you pick the therapy you think is best for them. In general, there's been a trend to shift toward higher-efficacy therapies, as long as they remain safe. But safety is always an ongoing issue. Safety concerns can develop years after a therapy is approved, and that would change the calculus of how you decide what to treat someone with.

It would be very nice if we had a biomarker that predicted treatment response. We don't have one yet. The best biomarker we have is actually looking for antibodies to JC [John Cunningham] virus as a predictor of risk of PML [progressive multifocal leukoencephalopathy]. But we don't have the metrics yet. We're looking at things like neurofilament light, which may be useful as a measure of therapeutic response. Those data are being accrued. MRI is helpful, but as I had mentioned earlier, we still don't have a way of quantitating it and saying that if you have this many lesions on this agent in 1 year, you should switch. We don't have that data yet.

The 2 main horizons that we're looking at now are neuroprotection—that is protecting the brain and spinal cord from degeneration—and repair—repairing the damaged nervous system. We have strategies looking at both. The repair strategies are very exciting. They potentially include using cellular replacement therapies, like mesenchymal-type stem cells, and molecules, which are being tested, that would enhance endogenous repair within the damaged nervous system. Early phase work, but it's very exciting.