New Paths and Expansions in Multiple Sclerosis Treatments

August 22, 2018

Darin Okuda, MD, spoke about the new investigative therapies for MS, as well as the expanding role of disease-modifying therapies.

Darin Okuda, MD

While disease-modifying therapies (DMTs) are a favorite for use in the treatment of multiple sclerosis (MS), especially since ocrelizumab proved efficacious in primary progressive MS, the role they play across the board has remained unclear, according to Darin Okuda, MD.

For one, the medical community’s eyes have become set on the possibility of myelin-repairing therapies. But their use is affected, really, by the overall added work and surveillance needed for the use of DMTs, Okuda said. Additionally, a lack of certain data may have an impact on the comfort of the general neurologist to use them.

The professor of neurology and neurotherapeutics, director of the Multiple Sclerosis and Neuroimmunology Imaging Program, director of Neuroinnovation, and deputy director of the Multiple Sclerosis Program and Clinical Center at UT Southwestern Medical Center, spoke with NeurologyLive to discuss the pipeline for MS, as well as the lack of clarity in the role DMTs should be playing in its treatment—and what’s exciting for him in the innovation space.

NeurologyLive: Based on what’s coming in the pipeline, is there anything you’re keeping your eye on or are excited about?

Darin Okuda, MD: The most exciting path for treatments for MS patients involves the myelin repair drugs. So, recombinant humanized-IGM 22 (rHIgM22) that was really founded by Moses Rodriguez, MD, a clinician-scientist at the Mayo Clinic Rochester. That compound is now being championed by Acorda Therapeutics and it’s currently under study. Biogen has their own version of it called opicinumab, also known as anti-LINGO 1, and that drug is also being studied actively as well. This is a new treatment path for us because these are therapies aimed at not modulating the immune system, but allowing for actual repair of myelin, and the ultimate protection of axons.

To add to the myelin repair list is the recent introduction within clinics the of the use of biotin, vitamin B7. There’s a lot of science that has gone on in Europe and a lot of talk about how biotin may actually help to facilitate mitochondrial behavior but may also play a role in self-myelin repair. There’s a company called MedDay, a French company, and they’re pretty much just selling biotin, and it’s a dose that is 30 times higher than what you can buy at Target, Walgreens, or Costco. Thirty times the highest over the counter preparation. It’s high dose biotin at 300 mg a day—100 mg taken 3 times a day—and it is acquired without a prescription on Amazon.

How is the role of DMTs expanding in MS? For the practicing neurologist, how are disease-modifying therapies being used for their patients?

DO: So, that part is unclear. From a general standpoint, I’m able to say that more of the classical agents are used in those settings—you have the use of Copaxone (glatiramer acetate), Avonex (interferon ß-1a), Betaseron (interferon ß-1a), Rebif (interferon ß-1a), and maybe some of the oral therapies. In academic centers, there’s more use of the ocrelizumabs of the world, the [natalizumabs], the [alemtuzumabs]. It takes a lot more work and a lot more surveillance. Maybe comfort levels differ as well. If you’re a general neurologist, it may be tough for one to fully advocate for a therapy that’s not well understood, and, a therapy in which they’re not necessarily keeping track of all the safety outcomes that are occurring from a week to week basis.

I think what’s really key here, though, is when it comes to the effective management of multiple sclerosis, that the earlier we can administer treatment the better the outcomes will be longer term, and a preventive approach is the most important aspect when it comes to MS care. Just because you’re on a therapy it doesn’t mean that you are for sure going to do well, but it does give you the best chance for the best outcome. Kind of like wearing your seatbelt. If you don’t wear your seatbelt when you drive, it doesn’t mean you’re going to get hurt, but it increases your chances of not getting hurt if you wear it and get involved in a car accident.

I think the other thing that needs to be underscored is not when it comes to the management of multiple sclerosis. It’s not just giving them effective treatments for the disorders. Ensuring that No. 1, they’re general health is optimized. You know, a lot of these patients are overweight, blood sugars out of control, they have habits like smoking. There’s emerging science to suggest that general health outcomes are more meaningful than some of the important factors that we have identified in multiple sclerosis before. So, that general health outcomes may be more meaningful then focusing on vitamin and mineral supplementation for MS patients.

In terms of primary progressive MS, what role are DMTs playing there?

DO: Well, we have 1 FDA-approved therapy for primary progressive multiple sclerosis, which is Ocrevus (ocrelizumab). There are a number of passionate opinions regarding the magnitude of the effectiveness of the agent within that cohort. The opinions are split whether primary progressive multiple sclerosis represents a continuum of disease, or if it indeed represents its own distinct genotype. So, we don’t have 100% agreement amongst specialists regarding that point. We know that early spinal cord disease can occur in individuals well before symptom onset. So, well before patients become symptomatic we know that spinal cord lesions can be present or can result from the immune system misbehaving. And, I think in the future you may see more manufacturers developing resources for progressive genotypes but is that really the right area of focus or should we really be focusing on primary prevention. Because, really the most effective drug for any progressive form of MS is a myelin repair and axonal repair agent, versus an anti-inflammatory agent.

Is there anything else you’d like to add?

DO: We should talk about how technology is playing a role in the management of all these, in the management of Multiple Sclerosis. I lead the neuroinnovation program at UT Southwestern, and it’s a program whose primary focus involves leveraging hardware, software, technology in an effort to create the next generation of patient surveillance metrics, diagnostic tools, all of the above. But, when you look at millennial medicine—we had a paper recently published on the treatment on millennial patients with MS—it’s very different than the historical cohorts that we’ve cared for before. How these younger groups of individuals are leveraging technology on their own is playing a key role, is having a huge impact with respect to the management of their condition. Because they may believe everything they read, they want to do things on their own, they make less eye contact with you in the clinic, they have a greater likelihood of being on their mobile phone during the visit. They do a lot of research beforehand, and they think they know how to manage their condition as well.

Transcript edited for clarity.