Regulatory

FDA poses some tough questions for GSK’s pitch to gain an approval for Nucala in COPD

GlaxoSmithKline faces a steep, uphill climb on Wednesday in its quest to gain an approval for Nucala (mepolizumab) as a therapy for COPD.

Already approved in asthma, top regulators at the FDA laid bare some big problems with the pharma giant’s application on COPD. And they plan to challenge a panel of outside experts on the company’s assertions that this IL-5 drug is ready for much wider use.

The key issues at the FDA, outlined in their internal review:

Hal Barron

For one, GSK’s drug $GSK failed one late-stage test while scoring a success in the other, according to the FDA memo presented by Sally Seymour and Banu Karimi-Shah at the Division of Pulmonary, Allergy, and Rheumatology Products. With only two Phase III studies in this indication, that leaves regulators considering an approval without support data from two well-controlled studies — the agency gold standard.

There was no dose response they could find in the two dosage arms.

The FDA added:

Some key secondary endpoints, such as time to first moderate-to-severe COPD exacerbation showed numerical trends favoring mepolizumab. However, there were no consistent and clinically meaningful differences in severe COPD exacerbation rate, FEV1, or SGRQ between mepolizumab 100 mg and placebo.

GSK’s trial designs spurred questions, with no baseline collection of asthma history — which could have influenced the outcome of the study. How will GSK properly define the patient population for this drug?

And then there’s safety:

As described in the Review of Safety, analyses by both the Applicant and the Agency revealed consistent imbalances in cardiovascular thrombotic events towards mepolizumab despite different analysis methods. Additional serious and non-serious adverse event imbalances are noted in the Review of Safety section of the briefing document.

It’s a bad week for GSK to be challenged. New R&D chief Hal Barron is expected to lay out his strategy on Wednesday, while the panel meets to consider if the research group at GSK handled the COPD program properly. After years of development setbacks, outside of HIV and vaccines, it’s these kinds of critical discussions that the pharma giant has to grapple with once and for all.

This application also presents a challenge for the FDA. At a time some critics are warning that the FDA has cut standards to a bare minimum, will they let another drug with questionable data out on the market?


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