12:00 AM
Sep 16, 2013
 |  BioCentury  |  Regulation

Lowdown on LABAs

How FDA uses dose-response curve to evaluate LABAs for pulmonary disorders

Although vilanterol looks poised to pass muster at FDA for a second time, companies working on products that contain a LABA should not view it as a sign the agency is no longer requiring companies to establish the lowest effective dose.

FDA last week told BioCentury it needs to see a well-defined dose-response curve that clearly identifies the lowest dose on the ascending portion of the curve.

In fact, that dose may not actually be the lowest dose with statistically and clinically significant activity.

The agency's comments came in conjunction with last week's meeting of the Pulmonary-Allergy Drugs Advisory Committee, which voted 11-2 that efficacy and safety data for Anoro Ellipta 125 µg umeclidinium bromide/25 µg vilanterol support approval for the long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

In May, FDA approved 25 µg vilanterol - a long-acting adrenergic receptor beta 2 agonist (LABA) - as a component of another product, Breo Ellipta, to treat COPD.

GlaxoSmithKline plc and Theravance Inc. have developed Breo and Anoro under a 2002 deal to develop compounds to treat asthma and COPD.

Leading up to the Breo decision, some analysts had suggested FDA might raise questions about data from a Phase IIb dose-ranging study of vilanterol in COPD patients, which were published in Chest in July 2012.

The data showed a statistically significant improvement on FEV1 using only half the dose of vilanterol that is contained in Breo and Anoro.

Moreover, the differences in FEV1 between each of the doses were less than 100 mL, which is generally considered to be the minimal clinically important difference (MCID) in COPD.

However, the partners' extensive clinical studies yielded a clear dose-response curve, and showed 25 µg was the lowest dose of vilanterol on the ascending portion of the curve.

Thus, when Breo came up for...

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