MannKind faces stiff skepticism in its third go at FDA approval

After two FDA rejections, MannKind ($MNKD) has returned with more data on its long-delayed inhaled diabetes drug, but regulators see Afrezza as anything but a slam-dunk case, raising questions over the treatment's safety and efficacy before a scheduled review.

In documents posted ahead of next week's meeting of the FDA's diabetes panel, agency staff acknowledged Afrezza's promise in treating Type 2 diabetes but voiced serious concerns about the drug's safety profile, pointing to risks of bronchial spasms and declining lung function. On the efficacy side, Afrezza proved itself better than placebo and non-inferior to injected insulins in lowering blood A1c levels at 24 weeks, but "the comparative efficacy shown here was not compelling," FDA reviewers wrote, noting that, "because of missing data, the robustness of this analysis is an issue."

Coupled with the safety issues, those concerns could sway agency advisers to recommend against Afrezza at their meeting April 1. The agency is not required to follow the opinions of its third-party panels, though it often does, and the FDA is known for holding diabetes treatments to particularly high safety standards. The agency set a final decision date of April 15 for MannKind's drug, but many analyst expect a delay due to the timing of the advisory meeting.

Whether Afrezza is due for a third rejection or a regulatory coronation remains the matter of much debate, but even if MannKind can finally follow through, the market potential of its setback-plagued drug is less than thrilling.

MannKind's hope is for its dry-powder formulation to contend with market-leading injected insulins from the likes of Eli Lilly ($LLY) and Novo Nordisk ($NVO), but those unimpressive comparative efficacy results that stood out to FDA reviewers are unlikely to help it win any potential market share. As the agency staff points out, despite top-line non-inferiority, Afrezza's 24-week mean reduction in A1c was actually statistically significantly worse than that of injected insulin.

The Valencia, CA, biotech has spent upwards of $2 billion on the now-7-year effort to get Afrezza approved, enduring rejections in 2010 and 2011 as the FDA demanded more data on the novel drug.

- read the FDA briefing (PDF)

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