Cladribine CIS study

“I was asked last night what was the highlight of the AAN 2013. Without a doubt the Cladribine CIS, or ORACLE, study. As you can see from the following graph cladribine treatment reduces the chances of a second attack, or developing clinically definite MS, by 67%; these are the best CIS results to date.”

“What is also very impressive is that after 1 year the cladribine treated subjects flat-line, i.e. very few people have a second attack in year 2. This may mean that cladribine takes time to have its maximum effect. I wonder what will happen if these cohort of study subjects were followed long term? May be those who haven’t developed MS by year 1 will never develop MS.”

“Could cladribine prevent the development of MS?”

“What is also clear is that there is no cancer signal in this study. I wonder what would happen if this data set was resubmitted to the European Medicines Agency? Would they still take a negative view?”

“Cladribine is not only an effective therapy, it is also a convenient therapy being given as tablets (10 days per year), it is well tolerated and has a good short to intermediate term safety profile. Cladribine is also rapidly cleared from the body so it is an ideal tablet for young woman wanting to get on top of their MS and start a family. Finally, it is an induction therapy and may not have to be given beyond year 2.”

“The ORACLE study is not only my AAN highlight, but also my low-light;  how could we let this drug die? Surely, MSers & CISers need to have the option of choosing cladribine for their MS?”

“The following is the full poster that was presented at the AAN. Professor Leist has given me permission to make it available via the blog.”

“It is interesting that an ORACLE is a person considered to be a source of wise counsel or prophetic opinions, or an authoritative or wise statement or prediction. Is the ORACLE study saying that we may be able to cure MS in a subgroup of MSers with induction therapy? Similar, to Alemtuzumab, we would need to wait 15 to 20 years to get an answer. Wouldn’t it be a tragedy if we ignored the ORACLE?”

: multiple

16 thoughts on “Cladribine CIS study”

  1. What are the similarities and differences between treating MS with Cladribine and rituximab? Why did Merck pull this drug from the market?

    1. Re: Why did Merck pull the plug? Please see earlier post on this targets both T and B lymphocytes and Rituximab B cells only. I suspect the real target of all these drugs is the B cell.

  2. Good news if you have RRMS. Do you think it is worth trying on SPMSers as is being done in the ASCEND trial with tysabri?

  3. Would a two year course of treatment constitute a lifelong effective treatment? Is this the implication of the Oracle study? I had one years treatment with Cladribine in Australia before it was pulled 20 months ago and have gone from approximately 5 relapses a year prior treatment to NONE since. If I had been able to continue Cladribine into the second year of treatment could it have meant that the MS could have been halted completely? Is there any follow up being done on people who have had one years treatment only? We were promised longitudinal follow up by Merck but that has also been dumped along with the drug which I find incredibly unethical. I have been bitterly disappointed that Cladribine was taken off the market. I have just started Aubagio but the efficacy is a bit low compared to Cladribine.

    1. I think cladribine could be a "reboot therapy" the idea was year 1 and year 2 ,like alemtuzumab studies, and wait and see if another course is needed may be it is not needed. Maybe one could be enough but I don't know the answer. Maybe Prof G knows more about follow up, etc.

    2. Two years of treatment may be enough. The idea would be to treat-2-target and only retreat if disease-activity resurfaces.

    3. I agree that it was unethical to pull cladribine from the market once it was launched. Big Pharma at its worst. You may be able to find a neurologist who is prepared to dose you with the oncology product off-license.

    4. Is that you Brog in Australia? I thought you said one of the reasons cladribine was pulled was that there was a 4% increase in cancer risk after 2 years. I can see that it is a very effective DMD, but perhaps Prof G can deal with this point. Is there a definable increased cancer risk, what is it, or is there insufficient data to say whether there is one?

    5. We don't have enough data re cancer risk that is the problem; it is a catch-22 without data you can't get approval and without approval you can't get long-term data to address the malignancy risk. Therefore the EMA and FDA decided against approval and the Company said it would take too long to do a trial to answer the questions therefore better to pull the plug on the programme. A very, very, sad state of affairs.

  4. Yes Anon of Monday 25 9.13 It is brog 🙂 You wouldn't own a Spanish cat would you?Not too many Cladribiners out there, are there? Bit hard to stay totally anonymouse.Yes, I was told that there was a potential risk of a 4% increase in the cancer rate above the non-Cladribine population with extended treatment which is why my treating neuro had planned to give me the 2 year initial treatment and then to follow it up with BG12. Sadly we are still waiting for BG12 so I am now on AubagioProf G, if Merck aren't even doing longitudinal follow up on the group that was on the PFP for one year how will the data re: cancer or other risks be obtained? I was dumbfounded that there is no follow up for us…..

    1. No.I've got 2 UK cats and I'm BP. I've got no idea about cladribine, but my son has had alemtuzumab. For those lucky enough to have had reboot treatment, the big question is , what comes next? Maybe BG12 is too much of an immunosuppressive to be considered for use with alem or cladribine- maybe we're looking at statins or laquinimod or some better neuroprotectant.

    2. Merck-Serono have asked all trial participants and MSers who have been treated with cladribine to be part of a safety register follow-up.

    3. Merck told us the longitudinal follow up was being discontinued…. and we have not had any follow up questions done as we were supposed to have had at 6 monthly intervals. Nothing at all since the drug was pulled. Anon from Aus

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