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Archive for March, 2011

Rigel’s and AstraZeneca’s R788 (fostamatinib) – an oral Syk inhibitor for rheumatoid arthritis

Posted by lifetech on March 30th, 2011

Rigel’s and AstraZeneca’s R788 is an oral, small molecule therapy in phase III rheumatoid arthritis (RA) trials. It modulates inflammation via inhibition of splenic tyrosine kinase (Syk). If successful, R788 will compete in a market currently dominated by biologics that inhibit TNF-α — all agents that are administered by injection or intravenous infusion. While a ‘pill’ would seem far preferable to a ‘poke’, particularly for a chronic disease, phase III trials still must show robust efficacy and an appropriate safety profile. The companies have reported data from all three phase II TASKi trials and have begun their phase III OSKIRA trial program. Of special interest, the TASKi3 trial results differed from those of the TASKi 1 and 2 trials. Our latest report explores the possible reasons for TASKi3’s failure and what that means for the ongoing phase III trials. The report also explores FDA guidance on RA drug development and the degree to which the ongoing phase III program meets those standards. Finally, phase II trials have identified some emerging safety signals which need further characterization. Thus, the question remains as to how much risk regulators, patients and the marketplace will accept in exchange for the convenience of an oral treatment for this debilitating disease.


BioMarin’s GALNS – enzyme replacement therapy for Morquio Syndrome A

Posted by lifetech on March 15th, 2011

BioMarin has built a portfolio of products for rare orphan conditions, which have proven to be valuable commercial opportunities despite targeting diseases with low prevalence. BioMarin’s latest product, GALNS, is an enzyme replacement therapy (ERT) currently in phase III testing for MPS IVA, a rare genetic disease also called Morquio syndrome A. MPS IVA causes severe disability and early mortality, and current treatment options are of limited benefit. However, similar diseases have been successfully treated with ERT, including two products developed by BioMarin itself: Aldurazyme for MPS I and Naglazyme for MPS VI. Thus, there is good rationale for developing ERT in MPS IVA.

In a pilot phase I/II study, GALNS showed evidence of clinical activity, as measured by biomarkers, respiratory function and physical endurance. But the trial was small and uncontrolled, so these early results must be confirmed in the ongoing placebo-controlled phase III trial. If phase III proceeds as planned, we anticipate top-line results in the third quarter of 2012. GALNS would make a fine addition to BioMarin’s ERT portfolio. Of course, regulatory success hinges on phase III outcomes, and the potential for commercial success will also depend heavily on GALNS’ clinical performance in a controlled trial. In our recent report, we explore these issues in greater depth.