FDA releases Ariflo briefing documents

Deliberations at Friday's meeting of FDA's Pulmonary-Allergy Drugs Advisory Committee will focus on the clinical relevance of the efficacy demonstrated in trials of GlaxoSmithKline's Ariflo cilomilast, and on the adequacy of the safety database, Badrul Chowdhury, director of the agency's Division of Pulmonary and Allergy Drug Products said in a memo released Thursday. GlaxoSmithKline (LSE:GSK; GSK) is seeking approval of Ariflo to treat chronic obstructive pulmonary disease (COPD) in patients with poor responses to albuterol. GSK's submission is the first NDA for a phosphodiesterase-4 (PDE-4) inhibitor.

In an extensive clinical program, Ariflo demonstrated modest efficacy, according to FDA's analyses. GSK ran four similarly designed pivotal studies. Statistically significant differences between Ariflo and placebo for the primary endpoints, maintenance of lung function as measured by FEV1 and decrease in the St. George's Respiratory Questionnaire (SGRQ) score, occurred in two of the studies. The SGRQ score change was clinically relevant in only one of the trials, according to FDA. The improvement in FEV1 among Ariflo patients in the two statistically significant trials was about 30-40mL. In a memo to advisory committee members, Chowdhury suggested that this should be compared to a mean improvement of 100mL typically obtained with theophyline, a non-specific PDE inhibitor. He also noted that GSK declined FDA's request to include a theophyline arm in the company's most recent pivotal Ariflo trial. ...