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Serono's Oral Cladribine for the Treatment of Multiple Sclerosis Awarded Fast Track Status by FDA

Serono announced today that oral cladribine has been designated a Fast Track product by the US Food and Drug Administration (FDA). This designation covers patients with relapsing forms of multiple sclerosis.
Serono's proprietary oral formulation of cladribine for the treatment of multiple sclerosis is currently being evaluated in a multi-center, multi-national Phase III study, CLARITY (CLAdRIbine Tablets Treating MS OrallY) . It is a two-year, double-blind, placebo-controlled study involving over 1,200 patients. Patient enrollment into this pivotal trial is planned to be completed by the end of 2006.

"We are very pleased that oral cladribine has been designated a Fast Track product," said Ernesto Bertarelli, CEO of Serono. "As a leader in multiple sclerosis, we are committed to providing new treatment options that can further improve the quality of the lives of people with this serious disease and our objective is to bring to them the first oral disease modifying treatment."

"Thanks to decades of research, there are injectible drugs available to treat some forms of MS, but there is certainly a need for more and even better therapies to treat all forms of the disease. Having an effective oral therapy for MS would be a major step forward in improving quality of life for people with MS," said Dr. John Richert, Vice President, Research and Clinical Programs, at the National Multiple Sclerosis Society.

Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Under Fast Track designation oral cladribine is eligible for Priority Review and FDA may consider for review portions of the marketing application before the New Drug Application (NDA) is completed.

About cladribine

Cladribine is a purine nucleoside analogue that interferes with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are involved in the pathological process of multiple sclerosis. Through its differentiated mechanism of action, oral cladribine may offer an alternative option to patients with multiple sclerosis.

Source: Serono International S A(21/09/06)

Could this be the real reason for the FDA fast-track? "While data do not support its use as a first-line MS treatment, cladribine may be a promising agent for refractory patients with secondary progressive MS."



Cladribine: An Investigational Immunomodulatory Agent for Multiple Sclerosis

Ann Pharmacother. 2006 Sep 19
Brousil JA, Roberts RJ, Schlein AL.
St. Louis College of Pharmacy, St. Louis, MO.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of cladribine, a purine analog undergoing Phase III trials for approval of its use in the treatment of multiple sclerosis (MS).

DATA SOURCES: A MEDLINE search (1966-September 2006) was conducted using the key words cladribine and multiple sclerosis. No limits were placed on the search.

STUDY SELECTION AND DATA EXTRACTION: Studies and review articles related to cladribine and MS were reviewed. The trials examining the role of cladribine in MS were analyzed.

DATA SYNTHESIS: Cladribine is a purine analog that demonstrates lymphocytotoxic activity. Recent data suggest that cladribine may have a role in the treatment of relapsing-remitting and the progressive forms of MS. In these studies, cladribine has shown mixed results in decreasing neurologic disability, as measured by various rating scales, but has consistently shown positive results in reducing the number of enhancing lesions, which reflects a measure of disease activity. To date, there is one ongoing study examining the role of oral cladribine in the treatment of relapsing-remitting MS. The incidence of adverse effects with cladribine has been significantly greater than with placebo, with the most common being myelosuppression.

CONCLUSIONS: While data do not support its use as a first-line MS treatment, cladribine may be a promising agent for refractory patients with secondary progressive MS. Further studies are warranted.

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Dignan,

I'm not sure what 'fast-tracking' means given that the Phase 3 trials have not completed enrolling. I can't see Phase III results out until end of 2008, so not sure why the FDA are making announcements at this stage.

I keep seeing the term 'refractory patients' and 'refractory MS' but haven't got a clue what refractory means.

Ian

It has been shown for years that lesions do not correlate well with impairment. The fact that the trial results do not show decreased neurological disability makes this pill pretty useless, in my opinion.

In these studies, "cladribine has shown mixed results in decreasing neurologic disability, as measured by various rating scales, but has consistently shown positive results in reducing the number of enhancing lesions, which reflects a measure of disease activity. "

gwa

Bromley, I just reread your initial post and it specifically says fast-tracked for relapsing remitting patients, so I guess my Pubmed abstract is unrelated.

I'm with you about refractory, I would have thought refractory would refer to a period between events where the body takes time to recover, but it doesn't appear to be the context in which they're using the term.

I've e-mailed one of my neuros who is overseeing a Cladribine study to ask him whether this treatment offers much more over the current DMDs apart from being in tablet form.

GWA,

You read my mind and I was a few seconds from posting exactly the same. Isn't it time these drugs companies ask the customer what they want? They seem to meet the needs of the researchers eg fewer lesions, fewer relapses, but as the end user, we want no disability, reversal of disability etc etc. It's the academic researchers who are running the show not the sufferers.

Ian

The only time I would fast track an MS drug is if I saw tangible, physical, clinical improvement in MS patients(PLURAL, meaning more than one). That justifies a fast track. How stupid to fast track something that hasn't been studied and who knows what if any benefit oral cladribine has. It sounds like marketing HYPE to me. BS


Brock

Maybe all of us here at Thisisms.com could get rich? Here is an idea...

Lets create a special pill. We can call it Sucavax, that sounds effective right? The ingredients will be SUGAR. We will have everyone at thisisms.com be in the clinical trial. We will see its safety profile through each of the stages. Remember, we will only use data that makes sucavax look like it has a "beneficial effect". If nothing else, we can rest on the laurels of the placebo effect, why not? The CRAB's do. We could do studies on mice, make them injest this sucavax, and record data from only the mice whos EAE took a less severe disease progression.

BINGO!!! You have a another drug!!! Then it would be CRABS, and we would all be rich like Serono, Glaxo, Biogen Idec, just to name a few.

Whos in???

I forgot to mention that once the safety profile was determined (and this is crucial), we would apply for FDA fastracking... It won't sell as good if we don't.

Brock

And don't forget the side effects:
weight gain
weight loss
diarrhea
constipation
headaches
drowiness
insomnia
sexual side effects
etc.................