This Is MS Multiple Sclerosis Community: Knowledge & Support

Dignan,

You''ll have to get up earlier to beat me.

Ian

http://www.mstrust.org.uk/news/recentst ... sp?id=2809

No fair - you have access to that British internet.

Thanks Ian, I don't want to get up that early. Those results look decent so far, and I'm glad to see the low dose works better. Hopefully the side effects won't be as bad with the lower dose.

Wow, I think this is great news, after all this time we may actually have a oral med and it looks like it is more effective than the injectables. I know we have some time, but I am already thinking do I make the switch when the time comes? Like I said we will have some time to think about the Pros and Cons, but isn't it great to even be able to think about that.

Dave,

I was told the FDA has given oral Cladribine fast-track approval, meaning FDA hearings on it should start sometime this year. I'm not too far from you (Mont. Co, MD); I think I might try to attend the hearings when they start.

The dosing schedule of this drug is interesting.

During the initial treatment period in Year 1, eligible subjects will be equally randomised by a central randomisation system to receive either a) cladribine at a low dose (0.875 mg/kg/cycle for two cycles + placebo for two cycles); b) cladribine at a high dose (0.875 mg/kg/cycle for four cycles); or c) placebo (four cycles). During the retreatment period in Year 2, subjects will receive either a) cladribine at a low dose (0.875 mg/kg/cycle for two cycles); or b) placebo (two cycles).

So what are these cycles? (the following is from the trial with interferon that is still ongoing, but I think it is still relevant)

A cycle is defined as daily administration given consecutively over 4 to 5 days. Subjects will receive 0.875 mg/kg/cycle. Cycles will be administered on Study Day 1, Weeks 5, 48 and 52 of the study.

So basically you only take this drug daily for 2-4 five-day periods per year.

Does anybody know something about the pricing of cladribine.

The drug has already been approved for leukemia for some time (whats the current price for a doese compareable to the MS regime?), how are patent issues adressed in such a case - does anyone know?

Thanks
--Frank

_________________
Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.

Dignan,

My impression is that the drug is given in cycles like that because it is an oral form of chemotherapy. So I don't think it is something you want to take everyday.

Stumbled on this:

Citi - Flash: Cladribine Efficacious in MS, But Some Issues Remain

Conclusion(s) - Today Merck KGaA released encouraging data from the 1,300 pt CLARITY trial testing the oral agent Cladribine vs. placebo in multiple sclerosis. The data shows the drug is more efficacious than interferons (but less than Tysabri), and could pose a threat to BIIB's MS franchise if approved. Further, Cladribine has a favorable dosing schedule of 5 tablets 2x or 4x a year, which compares favorably to Avonex's weekly subQ injections. However, the following issues remain in our view: 1) will one trial suffice for registration and 2) is there a malignancy signal?

Data Solid -At the high dose Cladribine showed 55% annualized relapse rate (ARR) reduction from 0.33 to 0.15 (p<0.001) and in the low dose it showed 58% ARR reduction from 0.33 to 0.14 (p<0.001). This compares favorably to an ~30% ARR reduction for interferons. However, Tysabri seems to be more efficacious, having shown in ph 3 studies, that 80% of patients on Tysabri remained relapse-free after one year (vs. 60% on placebo), and 72% remained relapse free after 2 years (vs. 46% on placebo, a 68% reduction in annualized rate of relapse).

Timeline and Approval - A filing is expected in the US and EU by mid-'09. It remains to be seen if one trial will be sufficient to file and if Cladribine will get priority (6 months) review time which could mean approval by YE. We also note that previous ph 2 studies with Cladribine tested the IV formulation in MS and not the oral formulation used in this study. Thus, it remains to be seen whether 1 ph 3 study will suffice for approval.
Safety - In terms of safety, there were no cases of PML or ITP. However, there were 4 caes of malignancy (1 - ovarian, melanoma, pancreatic and cervical) in the 889 patients taking Cladribine over two years (a rate of 0.45% for 2 years or 0.225% for 1 year). There were no malignancies in the placebo arm. As shown at ECTRIMS last year, there are concerns about bone marrow toxicity and reproductive issues, given that many MS patients are young women of child-bearing age.

dreddk, that is interesting stuff. I was wondering about cladribine getting approval with only 1 trial too. I figure maybe, as the first oral MS drug, it might get away with it if the side effects don't look bad. Time will tell.

Here's some more articles on Cladribine:

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http://www.news-medical.net/?id=108

Probably the reasons one trial is ok with the FDA is what Dignan said, that there's a big push for an oral med; and the fact that ther injectable form of Cladribine was trialled earlier.

Another interesting article:

http://www.biospace.com/news_story.aspx ... tyId=43519

Is Merck really trying to increase their sales, by adding Cladribine to Rebif?

The cladribine plus rebif trial reminds me...that's another reason they could get approval with the results from only one trial: because there is a second trial under way (with rebif). I think the same logic applies to the recently completed dirucotide trial where there are additional trials ongoing.