Cladribine results

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Cladribine results

Postby bromley » Fri Jan 23, 2009 5:46 am

Dignan,

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

Ian

http://www.mstrust.org.uk/news/recentst ... sp?id=2809
User avatar
bromley
Family Elder
 
Posts: 1887
Joined: Fri Sep 10, 2004 3:00 pm

Advertisement

Postby patientx » Fri Jan 23, 2009 8:07 am

No fair - you have access to that British internet.
User avatar
patientx
Family Elder
 
Posts: 1066
Joined: Wed Sep 10, 2008 3:00 pm

Postby dignan » Fri Jan 23, 2009 9:32 am

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.
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm

Postby daverestonvirginia » Fri Jan 23, 2009 9:49 am

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.
User avatar
daverestonvirginia
Family Elder
 
Posts: 179
Joined: Mon Apr 09, 2007 3:00 pm
Location: Reston, Virginia

Postby patientx » Fri Jan 23, 2009 10:08 am

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.
User avatar
patientx
Family Elder
 
Posts: 1066
Joined: Wed Sep 10, 2008 3:00 pm

Postby dignan » Fri Jan 23, 2009 12:53 pm

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.
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm

Postby Frank » Fri Jan 23, 2009 1:00 pm

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: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
Frank
Family Elder
 
Posts: 542
Joined: Wed Jan 03, 2007 4:00 pm
Location: Germany

Postby patientx » Fri Jan 23, 2009 1:25 pm

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.
User avatar
patientx
Family Elder
 
Posts: 1066
Joined: Wed Sep 10, 2008 3:00 pm

Postby dreddk » Fri Jan 23, 2009 9:50 pm

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.
User avatar
dreddk
Family Elder
 
Posts: 131
Joined: Sat Jan 20, 2007 4:00 pm
Location: South Pacific

Postby dignan » Sat Jan 24, 2009 10:41 am

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.
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm

Postby patientx » Sat Jan 24, 2009 11:48 am

Here's some more articles on Cladribine:

<shortened url>

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?
User avatar
patientx
Family Elder
 
Posts: 1066
Joined: Wed Sep 10, 2008 3:00 pm

Postby dignan » Sat Jan 24, 2009 1:25 pm

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.
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm


Return to Drug Pipeline

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users