FDA staff say GlaxoSmithKline, Theravance's Anoro Ellipta effective, but question safety data

In briefing documents released Friday ahead of an FDA advisory committee meeting on September 10, agency staff said that GlaxoSmithKline and Theravance's Anoro Ellipta (vilanterol/umeclidinium) showed strong efficacy at both doses in patients with chronic obstructive pulmonary disorder (COPD). However, the reviewers said that while the safety database for the once-daily inhaled therapy is fairly large, it is "not entirely conclusive, particularly in regards to cardiovascular safety."

In clinical studies, the companies compared Anoro to vilanterol alone and Pfizer and Boehringer Ingelheim's Spiriva (tiotropium). FDA staff noted that dropout rates in the trials ranged from 15 percent to 33 percent. The reviewers said that while patients given Anoro experienced improvements in lung function prior to dropout, they described GlaxoSmithKline and Theravance's assumption that the effect persisted after withdrawal as "implausible." Agency staff indicated that the overall cardiovascular safety profile of Anoro was unremarkable, but imbalances in specific subsets were identified, particularly for non-fatal myocardial infarction. The reviewers added that although no clear link to the therapy or specific doses was identified, "whether these imbalances and discrepancies constitute a safety signal when taken in the context of the complete development programme will be a topic for further discussion."

GlaxoSmithKline and Theravance filed for approval of two doses of Anoro containing either 125 micrograms or 62.5 micrograms of umeclidinium, both in combination with 25 micrograms of vilanterol. While the FDA staff said the companies’ dosing for Anoro was reasonable, the agency only asked advisers to consider the lower dose. Theravance's chief financial officer Michael Aguiar remarked "when you think about success for us, we really only need one" of the doses approved. "If we got one, that would be in line with our expectations. We did not file two expecting to get two," he added. For related analysis, see In Focus: GlaxoSmithKline's Anoro – can physicians be convinced sufficiently to drive drug towards blockbuster aspirations.

A final decision from the FDA on Anoro is expected by December 18, with analysts predicting that if approved, the product could generate peak annual sales in excess of $2 billion. The drugmakers filed an application for Anoro with European regulators in January. Similar drugs combining a long-acting beta agonist and a long-acting muscarinic antagonist are also under development by other companies, including Novartis' QVA149 (indacaterol/glycopyrronium). The therapy was recommended for approval in July by European regulators, and at the time Novartis said last it expects to file for FDA approval at the end of 2014.

GlaxoSmithKline and Theravance's COPD drug Breo Ellipta, which combines vilanterol with the inhaled corticosteroid fluticasone, was approved by the FDA in May, while a European application for the therapy remains under review. Analysts estimate that Breo could generate sales of $1.9 billion by 2018 (for related analysis, read Physician Views Poll Results – US Pulmonologists keen for Breo Ellipta – can payers be convinced?).

For further analysis of the LAMA/LABA market, see Physician Views Poll Results – LAMA/LABA market set to emerge rapidly; notable scope for twice-daily dosing.

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