Tim West, MD: Cladribine is interesting—it creates a couple of interesting dilemmas. It's a very interesting medicine because, from an adherence point of view, it's pretty great. You only have to take between 8 and 10 days of medicine a year, so for those patients that have a hard time with daily or twice daily medications, this might be something worth thinking about. In addition, the half-life on this is really short—it's about 24 hours. So, it's in and out of you in about a week, week and a half after stopping. I mean, if you look at the guidelines with regard to breastfeeding, they say 10 days after the last dose, then you're okay to breastfeed again. It's in and out of you pretty quickly, so that's also nice because it's not something that lingers.
The data, actually, in the clinical trials, the ORACLE trial and the CLARITY study, would suggest earlier is better but because of the safety profile, there is a boxed warning about malignancy and teratogenicity, so you don't want to be taking it if you're thinking about getting pregnant, or if you are pregnant for certain, or if you're actively trying to get pregnant. If you aren't using birth control, you probably want to avoid this medicine. Also, if you have any ongoing malignancy that you're struggling with, you probably would avoid this medicine. But aside from that, I think in any patient who has had a significant amount of activity, has failed some other medication either from tolerability or adherence or maybe just efficacy, I think it's a good option. The tricky thing is going to be finding that right balance for the right individual.
It's interesting because, again, if you look at the data, the studies were initially early on. So ORACLE was the CIS study, so people right at their very first attack, and they had a lot of benefit. It is very efficacious in that group. But it also carries with it this new active [secondary progressive multiple scleorsis] indication, and there are a couple of studies that would suggest that, as a surrogate marker, you could use an EDSS of 3.5 for secondary progressive. Remembering, if you look in the trials CLARITY was not a secondary progressive trial and neither was ORACLE, so they've never actually studied it in that specific population. But, if you separate out this idea of an EDSS of 3.5 and forward, it's shown pretty good efficacy in that group as well. I guess what I would say with this medicine is, if they failed something before or if they're getting worse, this is an option. It worked above 3.5 EDSS and below 3.5 EDSS, so it worked early or late.
One of the things that I think is worth thinking about with this medicine is that it is it's an induction agent. You give 2 doses and you don't dose it again in year 3 and year 4 because it can increase your risk of malignancy. So you're really giving it for 2 discreet doses—talking about 20 days of therapy, maybe 16 to 20 days of therapy over 2 years to get some durable efficacy. What's nice about it is that if you had a patient who can't get it together with their medicines, or if they just can't stick with a regimen, or they can't tolerate things, this is a medicine that, from a day-to-day, is pretty easy to tolerate and it's also a medicine that's pretty easy to adhere to. Then, you just have to watch out for the downsides, which is that malignancy risk, which is not nothing, but it's actually pretty small risk.