The vice president of US Medical Affairs in Neurology & Immunology at EMD Serono discussed the importance of having long-term and age-matched data on the use of the investigational oral agent in MS.
John Walsh, MD, the vice president of US Medical Affairs in Neurology and Immunology at EMD Serono
John Walsh, MD
At the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum in Dallas, Texas, EMD Serono presented a number of posters with updated data on cladribine, an oral tablet treatment for multiple sclerosis (MS).
The tablet is administered a maximum of 20 days over a period of 2 years, and thus far has shown consistent safety data and that No Evidence of Disease Activity-3 (NEDA-3) status can be maintained for up to 4 years post-treatment.1 To uncover more details from these data and discuss what clinicians need to know, John Walsh, MD, the vice president of US Medical Affairs in Neurology and Immunology at EMD Serono, spoke with NeurologyLive.
Walsh shared the key takeaways from the data, as well as the interpretation of the age-matched subgroup findings as they are related to the ongoing discussion surrounding the treatment of aging MS patients.
John Walsh, MD: At ACTRIMS, we presented some very interesting information which really characterized the long-term safety profile of cladribine, and we also talked about the sustained efficacy that we’ve seen, as well as some data for particular subgroups. In addition to that, the fact that we do have data in some patients now for up to about 10 years—particularly in terms of follow-up for safety—is something that is very important to us. It tells us a lot about a product that is not often seen at the time of approval. There’s a lot of really great information there.
To speak significantly on that—really, there were a few major things that we presented in terms of data at ACTRIMS, one being a poster about the durability of NEDA-3. We talked about the fact that No Evidence of Disease Activity is really defined by the lack of relapses, the lack of clinical disability progression at 6 months, and the lack of MRI lesions by the way of T2 or T1 gadolinium-enhancing lesions. The lack of development of those 3 factors being NEDA. It’s important that we show that at the end of our clinical trial, but the fact that we’ve now seen the durability to the 3- or 4-year mark as well? That we’re able to demonstrate that really underscores what we see in terms of the efficacy profile for cladribine.
We did an analysis on age where we did a cut off of multiple end points, based on the cut off of below and above age 45. There’s been some discussion recently in the MS literature about effects of certain medications and their ability to be effective in older versus younger sub-populations of patients, and again, we really don’t see any significant differences across multiple parameters when we use that cut off of age 45. That’s also been something that’s been very interesting to note.
From an efficacy perspective, we looked at the severity and frequency of relapses. Hospitalization and steroid use are good markers that people often look to in order to understand the severity of patients who are experiencing relapse, and this analysis looked at all of our relapses as a whole, but also in a post-toxic fashion in those patients who have use of steroids and hospitalization. We showed a >50% reduction, irrespective of steroid or hospitalization.
Then, last but not least, we had an updated safety analysis including up to 10 years of safety data follow-up in some of our patients. We have data from CLARITY (NCT00213135), the CLARITY-EXT (NCT00641537), and ORACLE-MS NCT00725985), in addition to our long-term PREMIERE study (NCT01013350). And again, this is pretty consistent with the safety data that we published to this point where we don’t see any new signals.
Now, aging in MS has really become a very hot topic, if you will, from 2 perspectives. One, from the perspective of what is the status of the immune system. What’s the status of the immune system in patients who are younger and older in MS? Then, the second question is: How that is changing, or is there a potential change in the immune system affected by therapy? That’s why it’s so hot right now.
But what we really saw is that—when you look at the cladribine tablet studies—they were efficacious in patients, regardless of age, with respect to reduction and frequency of relapse, the number of MRI lesions by T1 or T2 lesions, as well as NEDA-3. We saw that more patients were free from relapse and EDSS progression in the younger group than the older group, but that’s also consistent with the placebo groups as well. But across groups, no a major difference.
This is consistent with the previous analysis that we’ve seen in CLARITY. We did the age cut off at 50 years and we did the results of the overall study populations. For us, this really speaks to the fact that in those 2 cuts of data that we’ve done—in the 45-year-old cut off and 50-year-old cut off—we’ve really seen no major differences across groups. It does not speak to what the extremes in the elderly population are, and I don’t think many people if any have good data on that right now at all. But we’re reassured that we don’t see any difference when we’re going to break this group into 2 distinct age-matched groups.
1.Giovanonni G, Keller B, Jack D. Durability of NEDA-3 status in patients with relapsing multiple sclerosis receiving cladribine tablets: CLARITY extension. Presented at: ACTRIMS Forum; February 28 to March 2, 2019; Dallas, TX. Poster #3658. actrims.confex.com/actrims/2019/meetingapp.cgi/Paper/3658. Accessed March 6, 2019.