Good news! Some more competition for alemtuzumab? #MSBlog #MSResearch #NewsSpeak
“Good news, Merck has just announced that it is reapplying for a marketing authorization for cladribine from the EMA.”
“I am a big fan of induction therapy, which is why the resurrection of cladribine as a MS treatment is so important to me. The clinical efficacy of cladribine has never been in doubt. Now that the short to intermediate term risk of secondary cancers has been shown to have been driven by the placebo arm of the CLARITY study being an outlier (zero cases) rather than active treatment group being high; redefines the benefit:risk of cladribine. There is little evidence that cladribine increases short- to intermediate -term cancer risk. In addition, since the licensing of alemtuzumab as a 1st-line therapy the regulatory environment has changed. I am sure the regulators will now have a hard time saying no to a cladribine resubmission given that they have recently licensed alemtuzumab for relapsing MS defined clinically or on MRI.”
“As far as induction therapies go cladribine tablets are very easy to use; depletion is slow and gentle therefore there is no cell lysis syndrome that you see with alemtuzumab. More importantly the repopulation kinetics of the lymphocyte populations are completely different with cladribine compared to alemtuzumab. There is no B cell overshoot, which may explain the absence of secondary autoimmunity with cladribine. In short cladribine’s safety profile as an induction therapy is so, so, much better than alemtuzumab.”
“Good news, Merck has just announced that it is reapplying for a marketing authorization for cladribine from the EMA.”
“I am a big fan of induction therapy, which is why the resurrection of cladribine as a MS treatment is so important to me. The clinical efficacy of cladribine has never been in doubt. Now that the short to intermediate term risk of secondary cancers has been shown to have been driven by the placebo arm of the CLARITY study being an outlier (zero cases) rather than active treatment group being high; redefines the benefit:risk of cladribine. There is little evidence that cladribine increases short- to intermediate -term cancer risk. In addition, since the licensing of alemtuzumab as a 1st-line therapy the regulatory environment has changed. I am sure the regulators will now have a hard time saying no to a cladribine resubmission given that they have recently licensed alemtuzumab for relapsing MS defined clinically or on MRI.”
“As far as induction therapies go cladribine tablets are very easy to use; depletion is slow and gentle therefore there is no cell lysis syndrome that you see with alemtuzumab. More importantly the repopulation kinetics of the lymphocyte populations are completely different with cladribine compared to alemtuzumab. There is no B cell overshoot, which may explain the absence of secondary autoimmunity with cladribine. In short cladribine’s safety profile as an induction therapy is so, so, much better than alemtuzumab.”
“Having thrown the baby out with the bathwater it looks as if the baby is alive and kicking and threatening once again to disrupt the market; at least the induction side of the market for those who favour induction treatments over maintenance-escalation therapies. Maybe it’s time for us to run a head-2-head of alemtuzumab vs. cladribine in the NHS? It would have to be a non-inferiority trial; trying to prove that one drug is better than the other may prove too expensive and difficult.”
CoI: multiple, Prof G was the principle investigator on the CLARITY study
The Australians are going to be thrilled; when I did my lecture tour there on sabbatical they all complained about how much the missed having cladribine as a treatment option. There is nothing like real-life experience to drive change.
As an Australian who was diagnosed after cladribine was nixed and then waited for alemtuzumab, I wonder how that first convo with my neuro might have gone. Might have saved me a couple of years of uncertainty. Great news though, wonderful to see more options coming to market (again!).
On the most somber day here in the U.S. this and good and welcome news. Thanks for sharing this exciting information with us. Cathy Chester
How long will it take to actually get it to market?
First depends if EMA approves and also where they are in terms of manufacturing as this takes time too
I ask this question, I have beard Prof G mention many times that he believes Alemtuzumab has the potential to be a cure. Does Cladribine in your opinion over the same potential? Or are you biased because this was your drug and it got nixed the first time. The trial data I have seen is only 2 years, hardly a fair comparison…
The 2 year phase II data shows that NEDA was better for cladribine than alemtuzumab and the 4 year data (2 year extension of CLARITY was published as a poster at AAN in 2013 or 2014 and shows that NEDA was pretty good but as profG s an author he can best answer this.
How long does the process usually take once a company has made an application for a licence?
I guess a year based on other drugs but it depends when the meeting with EMA occurs.
Docs, seems that Cladribine could be a game changer; short oral dosage, very few collateral effects, very high efficacy.All the advantages of the newest oral therapy combined with best in class efficacy of the best known induction (infusion) therapy.Will be possible to switch from moderate efficacy oral therapy to cladribine as soon it reachs the market?Probably a lot of people would choose for an induction therapy, without the dangerous collateral effects of the present one.Or do you see it as a chance for new diagnosed only?
Could Prof G respond to this blogpost from 2011: this neurologist felt that Merck was too casual about safety concerns, otherwise Cladribine would have made it through the process.https://drsamhunter.wordpress.com/2011/06/26/goodbye-cladribine-%E2%80%93-the-rise-and-fall-of-a-promising-treatment-for-ms/"The investigators (including the distinguished Dr. Gavin Giovannoni in London and Stuart Cook in New Jersey) repeatedly and publicly ignored the existing literature on this risk, and effectively snubbed those physicians with scientific questions on how to address this issue. Moreover, it appeared that the trial was inadequately planned for careful follow up of this issue, so a clear answer was unlikely to be quickly obtained."
RE: ""The investigators (including the distinguished Dr. Gavin Giovannoni in London and Stuart Cook in New Jersey) repeatedly and publicly ignored the existing literature on this risk, and effectively snubbed those physicians with scientific questions on how to address this issue. Moreover, it appeared that the trial was inadequately planned for careful follow up of this issue, so a clear answer was unlikely to be quickly obtained."The issues were far more complex than ignoring the existing literature; I could write a book on this and will keep the material for my memoirs.