Amylin Symlin Complete Response Follows “Emerging Consensus” On Hypoglycemia
This article was originally published in The Pink Sheet Daily
Executive Summary
Response to second “approvable” letter includes re-analysis of hypoglycemia data showing lower rates of medically-assisted hypoglycemia in type 1 and 2 diabetes patients compared to overall rates in pivotal studies, Amylin says.
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Amylin expects its hypoglycemia re-analysis to mitigate FDA's concerns about its pending antidiabetic Symlin , the company says. Amylin's complete response to FDA's December 2003 "approvable" letter for Symlin (pramlintide) includes re-analysis of hypoglycemia that follows current thinking on the adverse event, VP-Clinical Affairs Orville Kolterman, MD, told a Sept. 20 analyst call. The analysis is "in line with the emerging consensus of the importance and accuracy of defining severe hypoglycemia as events requiring medical assistance," he stated. Amylin said it submitted the complete response Sept. 17 and expects a six-month review. Hypoglycemia has been one of the key review issues forSymlin, which was originally submitted in December 2000. FDA issued its first approvable letter in October 2001 after an advisory committee recommended against approval due to hypoglycemia concerns. The initial letter requested a dose titration trial; Amylin submitted the trial in June 2003. The second approvable letter requested "additional clinical data to identify a patient population and method of use for Symlin where there is no increased risk of significant hypoglycemia or where there is an added benefit that clearly counterbalances any potential for increases in episodes of hypoglycemia," Amylin said. In the six-month pivotal studies for type 1 and type 2 diabetes patients on insulin, Amylin reported overall hypoglycemia rates compared to placebo of 25% vs. 18% in type 1 and 9% vs. 6% in type 2. The company's re-analysis reports hypoglycemia event rates annualized for patient-years of exposure. Additionally, "the presentation in the complete response now compares severe hypoglycemia by two three-month periods," Kolterman noted. The original NDA analyses examined an initiation period (0-4 weeks) and a maintenance period (4 weeks to study end). For the type 2 diabetes trials, Kolterman reported annual hypoglycemic event rates of 0.06 for placebo vs. 0.09 for Symlin during months 0-3. For months 3-6, Symlin's rate was 0.02 vs. 0.07 for placebo. In type 1 diabetics, event rates were 0.19 for placebo vs. 0.5 for the first 3 months. For months 3-6, Symlin's rate was 0.27 vs. 0.24 for placebo. According to the re-analysis, the incidence of hypoglycemia was "lower than the overall rates originally reported in the type 1 studies and…no different from placebo in the type 2 studies," he concluded. Kolterman also reported results from a six-month, open-label clinical use study in which "the risk of severe medically-assisted hypoglycemia was found to be consistent with that seen in patients assigned to placebo in the pivotal trials." - Lee Szilagyi |