While attending the 2018 American Academy of Neurology meeting in Los Angeles, California, Medscape contributor Andrew N. Wilner, MD, interviewed Thomas Leist, MD, about his research into the long-term benefits of cladribine for patients after a first attack of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Dr Leist is professor of neurology and director of the Comprehensive MS Center at Thomas Jefferson University in Philadelphia, Pennsylvania.
Andrew N. Wilner, MD: Dr. Leist, tell us about the cladribine research you are presenting at this meeting.
Thomas Leist, MD: I have been involved for many years in the clinical trials of oral cladribine for patients with MS, particularly the ORACLE study. At this meeting, we are presenting an extension analysis of this study.
The ORACLE study was a first-event trial; it enrolled patients within 75 days after a first attack consistent with potential MS. Patients were randomly assigned to receive two different annual courses of oral cladribine or placebo. For patients in the active treatment groups, we saw more than 70% reduction of conversion to clinically definite MS (CDMS).
We also saw a significant reduction of conversion to 2005 "McDonald Criteria" for MS, meaning development of a new lesion. We also looked to see whether patients would fulfill the newer 2010 criteria for MS. It was clear that those patients who had true CIS and patients who fulfilled criteria for the diagnosis of MS at the time of the first event, by the more recent diagnostic criteria, had significant benefit from the medication, both on clinical outcomes and MRI outcomes.
In this new study, we looked at the available data beyond the 2-year treatment period. These data indicated that patients who have been treated with two cycles of cladribine have an attenuation of the disease course over a longer period of time. This raises the question of whether there are other potential medications for MS that don't have to be given as a continuous treatment but may be given more intermittently. It also raises the issue of potential early intervention with an drug and re-treatment when there is an appearance of disease activity in these patients.
Another agent in this arena that may play a similar role would be alemtuzumab, where we give two cycles and then re-treat if patients have disease activity or we assume from symptoms that they have disease activity. This is a concept of treatment that is somewhat distinct from the traditional MS treatments where we give ongoing therapy, be it daily, every other day, three times a week, or every 6 months.
Wilner: Is cladribine available? Has it been approved by the US Food and Drug Administration (FDA)?
Leist: Cladribine was submitted to the FDA and the European regulatory agency in 2010/2011. The submission was made on the basis of one trial, the CLARITY trial. At the time, it was not given approval because of concerns regarding potential oncologic risk; the CLARITY trial demonstrated a slight asymmetry of oncologic risk. That was the only trial to indicate such risk.
The data that are available for cladribine include CLARITY, the ORACLE study that we just talked about, the CLARITY extension, and the PREMIERE Registry of patients who have participated in clinical trials of cladribine. When you consider all of these data, no excess oncologic risk has been identified. It appears that the original CLARITY study was somewhat asymmetric in terms of oncologic risk because the placebo cohort included no oncologic cases whereas the treated cohort did. Thus, if you have a small molecular entity, this shows that you need to conduct at least two clinical trials.
To the best of my knowledge, cladribine is available in the European Union, in Canada, and in Australia. It may also be available in Russia. It is not yet available in the United States. I don't know when the manufacturer of the medication will submit it to the FDA.
Wilner: Would it be submitted for this very specific indication of halting progression of MS?
Leist: The CLARITY study included patients with relapsing-remitting MS. In the extension arm, patients were re-randomized regardless of whether they had disease activity during the first 2 years. The ORACLE study was in patients with early MS or with CIS. Ideally, this is an agent that will be available to large swaths of patients with relapsing forms of MS, including the patients with CIS or at-risk patients. What is different is that, rather than continuous treatment, this will be a treatment that is given in cycles.
Wilner: This is very exciting for patients with MS to have a pill that they only need to take a few times a year. That would be revolutionary.
Medscape Neurology © 2018
Cite this: Andrew N. Wilner. An 'As Needed' Treatment for MS? - Medscape - May 30, 2018.