FDA questions Firazyr endpoint

FDA said in briefing documents posted ahead of Thursday's Pulmonary-Allergy Drugs Advisory Committee meeting that overall results for the clinical program for hereditary angioedema (HAE) candidate Firazyr icatibant from Shire plc (LSE:SHP; NASDAQ:SHPGY) are "supportive of efficacy." However, the agency expressed concern with the use of the Visual Analog Scale (VAS), a patient-reported outcome instrument, to evaluate the primary endpoint of time to onset of symptom relief. Shire is seeking approval for self-administration of subcutaneous injections of the selective peptidomimetic bradykinin B2 receptor antagonist to treat acute attacks of HAE.

In the documents, FDA noted the Phase III FAST-1 and FAST-2 trials submitted in the original NDA for Firazyr used a single-symptom VAS, while the Phase III FAST-3 trial, which was included in a response to a 2008 not approvable letter, used a composite, three-symptom VAS. The agency said that while the studies appear supportive, changes in single-symptom VAS or the composite VAS are "not entirely intuitive" and the clinical significance of these changes is "open to interpretation." ...