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.
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?
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.
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?
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