Replies to post #114794 on Biotech Values

[orangeone]

Copaxone review article (may require subscription), reference below.

It goes over the various observed effects, as an altered peptide ligand, effect on regualtory T cells, APCs, and various clinical studies.

Whatever the case, change in doses and schedules of immunomodulators can have major consequences, so i cannot imagine how the 40mg producte would not require extensive studies.

Excert:
Possible mechanisms of action of GA. GA acts directly on APC to modify them into noninflammatory type II cells (1). GA is processed by APC (2) through class I (cross-presentation; 3) and class II (4) presentation pathways and is presented to CD8+ and CD4+ T cells, respectively. A robust CD8+ T cell response is either enhanced by or results in killing/modification of APC subsets (5). Presentation by modified APC results in generation of CD4+ Treg (6). Direct killing of Th1 CD4+ T cells results in deviation toward Th2 responses (7).



J Immunol. 2011 Feb 15;186(4):1887-90.

Glatiramer acetate treatment of multiple sclerosis: an immunological perspective.
Racke MK, Lovett-Racke AE.

Department of Neurology, The Ohio State University Medical Center, Columbus, OH 43210.

Abstract
Glatiramer acetate (GA) has been used as an immunomodulatory agent for the treatment of relapsing-remitting multiple sclerosis (MS) in the United States since 1996. It is currently one of two first-line agents for use in the treatment of relapsing-remitting MS. GA was the first agent to be used in the treatment of MS that was developed using the animal model of MS called experimental autoimmune encephalomyelitis. In this commentary, we examine the development of GA as a treatment for MS and discuss its mechanism of action as suggested by recent studies using modern immunologic methods.

[DewDiligence]

Teva completes enrollment of GALA phase-3 trial for thrice-weekly Copaxone:

http://finance.yahoo.com/news/Teva-Completes-Enrollment-in-bw-1437582157.html?x=0&.v=1

This international Phase III trial in patients with relapsing-remitting multiple sclerosis (RRMS), is designed to examine the efficacy, safety and tolerability of 40mg COPAXONE administered three times a week compared to placebo. The primary endpoint of the trial is the total number of confirmed relapses during a 12-month placebo-controlled phase, which will be followed by an open-label extension phase [this is significant—see discussion below].

Patient enrollment was completed in May 2011, recruiting over 1,400 patients at 180 sites in the United States, Europe, Central Eastern Europe and Israel. Results from the trial are expected in the second quarter of 2012.

Teva is once again being disingenuous, IMO. Copaxone dosed at 40mg thrice weekly will almost certainly be efficacious, but it may not be as safe as ordinary daily Copaxone dosed at 20mg. Hence, the FDA will probably not entertain an NDA for thrice-weekly Copaxone until all of the safety data are in hand.

Although data for the primary efficacy endpoint will be available in 2012, as noted in Teva’s PR above, the open-label safety portion of the study is expected to run until May 2014 (http://clinicaltrials.gov/ct2/show/NCT01067521 ). Thus, thrice-weekly Copaxone probably won’t reach the US market until 2015 at the earliest.

Note: Teva discontinued development of daily 40mg Copaxone in 2008 when it failed to show superiority to regular Copaxone (#msg-30498483).