Friday, October 26, 2007

Study: More on immunosuppressants and...

Okay... so what have we here:
1) Something that's supposed to be better than cyclosporine or tacrolimus
and
2) Another plug for that drug-plug thingymabob.

I'm not sure the "can be highly effective in... dry eye syndrome" bit is simply referencing the known use of cyclosporine in dry eye or whether they're hinting that after ISA-247/LX-211's succesful clinicals for uveitis they're going after the dry eye market (note all these 'wider therapeutic window' comments). Time will tell.

Next-generation calcineurin inhibitors for ophthalmic indications.
Anglade E et al, Expert Opinion on Investigational Drugs, 2007 Oct;16(10):1525-40

Calcineurin inhibitors (CNIs) are potent immunosuppressants that reversibly inhibit T-cell proliferation and prevent the release of pro-inflammatory cytokines by blocking the activity of calcineurin, a ubiquitous enzyme that is found in cell cytoplasm. CNIs can be highly effective in immune-mediated ophthalmic diseases such as uveitis, dry eye syndrome and inflammatory blepharitis, as well as for the prevention of rejection in corneal transplants. ISA-247/LX-211 is a novel CNI that is in Phase III clinical development for the treatment of various forms of non-infectious uveitis. ISA-247/LX-211 is a rationally designed analog of ciclosporin A that exhibits more predictable pharmacokinetic and pharmacodynamic properties and a 4-fold greater calcineurin inhibition than its parent compound, ciclosporin A. ISA-247/LX-211 has been observed to be effective, well-tolerated, and safe in early clinical trials, exhibiting a much wider therapeutic window compared with classic CNIs, such as ciclosporin A and tacrolimus. An alternative approach to widening the therapeutic window for the therapy of ophthalmic disorders lies in local delivery of CNIs through polymeric implants that release the drug over long periods of time. The silicone matrix episcleral implant LX-201 is in Phase III development at present for the prevention of rejection in high-risk cornea transplantation.

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