Hauser, who is director of the UCSF Weill Institute for Neurosciences, spoke with NeurologyLive about the gravity of the phase 3 ASCLEPIOS I and II trial results in relapsing MS.
Stephen L. Hauser, MD
While some might think the multiple sclerosis (MS) treatment landscape has become crowded, Stephen L. Hauser, MD, believes there is still room for improvement. Hauser, who is the director of the UCSF Weill Institute for Neurosciences, recently presented data on ofatumumab, a fully-human antibody targeting CD20+ B-cells, which may just fill that need. Data from the phase 3 ASCLEPIOS I and II trials
, presented at ECTRIMS 2019
in Stockholm, Sweden, demonstrated superiority over teriflunomide and what Hauser called an "unprecedented treatment effect" in relapsing MS.
sat down with Hauser to discuss the gravity of the data, and to learn more about where this investigational therapy might fit into the MS armamentarium.
NeurologyLive: What do you feel are the most significant takeaways from the ofatumumab data?
Stephen L. Hauser, MD
: I think the stunning effect size against the relapsing focal inflammation of MS is what was so remarkable here, in a drug that can be self administered by subcutaneous injection, rather than requiring an infusion. This is also a fully human antibody that has a side effect profile that was difficult to distinguish from sham injections.
One novelty of this study was that it featured a new type of that assay that can measure neurofilament in serum. It can be measured in the spinal fluid when nerve cells die, but until recently, we haven't been able to measure it accurately in blood. What we saw in the study was a dramatic fall in abnormal neurofilaments in the bloodstream;, it was apparent at the first blood draw and persisted throughout the study. So it was really true that fewer nerve cells were dying.
How do these latest trial results contribute to the growing argument for initiating more effective treatment earlier in the disease?
I think that our whole community will need to consider a new model of care, where instead of starting with less effective treatment, then moving up to slightly more effective treatments, and then moving up to the most effective treatments, we begin with the most effective treatments to maximize protection against inflammation and brain damage at the earliest point in the disease. And we now can do that, because we have a class of drug that is so well tolerated and has a safety profile that makes it a reasonable option in people whose disease has just started. Everything that we've learned about these drugs, is that they are even more effective when used early. I think across autoimmunity, we will probably be moving from a gradually advancing treatment model to a model like the way we treat cancer, with induction and then monitoring.
Given that ofatumumab is a self-administered subcutaneous injection, what do you feel are the benefits and drawbacks compared to other CD20-targeting therapies on the market?
I think one advantage is that patients and insurers are spared the cost of infusions, which can be extremely costly. Also, because ofatumumab is a fully human molecule -- the only fully human CD20-- it is potentially better tolerated over the long term. The mode of administration is probably a formula that many patients will like; they can take the drug by themselves just once a month. A problem that we have in treating people with chronic illness, especially young people, is that there's a lot of non-compliance, so there is an advantage with an infusion because you can be certain that the patient really administered the drug. But I think that if the final data look like the top line data, which I suspect it will, and the 2 drugs are reasonably similar in terms of their effectiveness, I think that they are 2 good options that patients can choose from.
The MS armamentarium has so many options now; what do these data mean for disease management? How do you think the neurology community will react?
I think that the effect size, the size of the benefit is extremely unprecedented -- it may be close to unprecedented in medicine. It is truly a feel good story for people with MS and for the science of medicine. Ms is one of the great success stories in healthcare, and these results suggest that we can even do better. When the data was presented at ECTRIMS, I could feel the rumble in the auditorium, it was palpable. Neurologists don't normally behave that way, so I think there is great excitement about this.
Transcript edited for clarity.