Refocusing the Multiple Sclerosis Treatment Landscape

Edmund Pezalla, MD, MPH, CEO of Enlightenment Bioconsult, formerly of Aetna, discusses treatment options for multiple sclerosis (MS), highlights results from the ASCLEPIOS I and II studies, and notes why this data can be useful for payers. Dr Pezalla is a payer strategy and market access consultant and a former pediatrician. 

Can you highlight the main challenges of treating MS?

One of the biggest challenges is finding a drug that works for a particular patient, that it has an acceptable efficacy and safety profile at the same time.

There are some medications that are more difficult to take, either because of the route of administration, or because of adverse events, or certain tolerability issues. These matter a lot to the patients, and they really have very strong feelings about some experiences that they’ve had, so they really look to those issues. At the same time, they want to find a drug that they can take that is the most efficacious, and will look at some of the clinical trials and what efficacy really means, but it’s now gone beyond just relapses  so both providers, the neurologists who care for MS patients, and the MS patients are really considering many other outcomes.

Other concerns include the coinsurance or copays needed to cover these medications. They can be expensive, and MS can influence the patients’ ability to earn a living wage, to maintain full time income.

Can you describe the main outcomes from the ASCLEPIOS I and II studies, which reviewed the safety and efficacy of ofatumumab?

The ASCLEPIOS I and II studies went over about a 30-month period, for over 1800 patients. They’re twin studies that evaluated the same types of patients and endpoints. These were patients with relapsing MS, and with disability scores of between zero and five.

The study’s primary outcome was like the primary outcome of almost all MS trials, which is the annualized relapse rate. It showed superiority in the annualized relapse rate reduction over an active comparator, the oral medication of the teriflunomide, and it also showed that patients did not progress as quickly in disability.

Reduction in disability did not quite meet statistical significance, but it had an impact on disability over the course of the study, as measured at 3 and 6 months and later in the study as well.

It also had a statistically significant impact on size of lesions by scanning, as well as the appearance of new lesions, which would indicate that there was significant improvement in reduction of inflammation in the brain.

These are all important things to find in a study these days in the modern world with MS because we’re really getting beyond annualized relapse rates. Relapse rates have been very low for a while. It is not good to have relapse at all, so it is great to have a new medication that has even lower relapse rates.

We are now looking much more at progression of disability, and this is especially important as patients move along in the MS journey where relapses become somewhat less important and less frequent, but where disability begins to pick up. Some of that can also be predicted by the scans, and showing that there’s reduced lesions, reduced number of lesions, or no new lesions. This leads to having some prediction for how patients are going to progress in the future.

How will the results of these studies be applied in a clinical practice setting?

The neurologists and other specialists who treat MS will take this very seriously. Reduction in relapse rates is really important, and as I mentioned, they are very, very interested in disability, so this is going to be a new tool for them to treat patients.

It could indeed be a first- or second-line therapy, and there might be, with the big improvement here in lesions, some movement towards making this closer to first line in terms of treatment, because there may be overall beneficial effect in having the patient on this medication early on and for a longer period.

I think that neurologists will take this very seriously, and will work with patients to determine which patients probably should move to this medication if they’re having any difficulties with their current meds, or may discuss it with patients who have new onset disease, or perhaps more severe new onset disease.

There will certainly be issues around coverage because there are other medications that are already covered as first line therapy, and there may need to be some realignment for that.

This is a possible candidate for earlier line therapy because it’s not an IV. As a subcutaneous medication, neurologists and patients are quite familiar with its delivery, and it’s something that the patient can do for themselves at home.

Why are these results significant for payers or other stakeholders?

It will cause payers and many others, including those who will consider guidelines or various sorts of policy, to consider reassessing the MS landscape.

We have a number of effective agents in terms of reducing some of the brain findings and reductions in relapses with medications, but we now have a number of medications that seem to be pulling away from the rest of the pack in terms of important measures, and we now have more of a focus on the disability measures.

I think we’re going to start to rethink this landscape. Which medications probably need to be held in reserve for those patients, and you need something that’s more active but, at the same time, might have more side effects or risks, at the same time moving ahead with more efficacious therapies that are also safe and have fewer safety and tolerability concerns.

Some older medications that though they may be effective and perhaps some patients prefer to stay on them perhaps will be less used in the future.

I think that this will cause us all to rethink how we manage MS drugs, whether we create step edits or other things that sequence the medications and which drug should be available. That parity is without consideration for cost or trying to put one in front of the other, so that we have a proper way of medications for doctors and patients to make choices.

Is there anything you would like to add?

I think we are moving ahead in MS, but this might be a point at which we could benefit from a broad view of what is available to treat individual patients, because we have many different mechanisms of action.We have many drugs that have benefits in one place, perhaps relapse rates vs benefits in another, like disability, or like reduction in the change in brain volume or lesions. This would be the time for a meta-analysis, possibly leading to some sort of real-world observational study of multiple medications in an attempt to identify which medications are right for which kinds of patients. That is, can we sort relapsing MS patients into categories based on what we think will be the most efficacious therapies for them.

I think that’s where we need to go next, because we have a lot of therapies that have been shown to be efficacious. Now we need to know who should receive each of those.