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Post Exubera, inhaled insulin has been an uphill struggle with regulators.
Alfred Mann, founder and CEO, MannKind
Post Exubera, inhaled insulin has been an uphill struggle with regulators. Alfred Mann and MannKind are nonetheless determined to push Afrezza, an ”ultra” rapid-acting mealtime insulin, over the regulatory peak and into the market. Will they succeed, or is MannKind doomed to play Sisyphus on mount FDA?
It would be in large part due to the efforts of Alfred Mann, CEO, founder and patron of MannKind, the Valencia, California-based biopharma, if Afrezza finally receives FDA approval next year. But an equally important question is whether, if Afrezza is approved, it will actually be prescribed by physicians and used by patients.
On August 14, MannKind presented the results of its two Phase 3 Affinity trials, both of which FDA requested in a Complete Response Letter issued in 2010. Now that the dust has more or less settled around those data – on August 26 the company posted an unusually frank FAQ, in response to analyst questions on a conference call – the consensus from the analyst community on Afrezza’s approval likelihood seems to rest somewhere between yes and perhaps.
Al Mann was less ambiguous, in a phone conversation with PharmExec. “I would expect it to be approved in mid-April ,” says Mann. “On our schedule it looks like April 14, but it could be a few days before or after.” Mann says his company will file in Europe shortly after completing the US submission. Mann says other markets are looking to the FDA and EMA as a guide on this product; however, “a number of countries are talking about approving [Afrezza] simultaneously…and one country is even talking about doing it before the US.” Which country is that? Mann wouldn’t say.
As for the question of whether physicians and patients, and payers, for that matter, will be keen to trade a syringe for an inhalation powder, Mann is typically optimistic that many patients will want to switch, although other opportunities exist as well. Hakan Edstrom, MannKind’s president and chief operating officer, says the company has done “extensive research in both Europe and the US” on physician preferences, confirming that physicians see Afrezza “as an additional tool in the armamentarium of treatment options. It doesn’t necessarily have to replace something else” to be successful, says Edstrom.
Hakan Edstrom, president and COO, MannKind
On the payer side, Edstrom says MannKind is currently working with Kantar Health, a data firm. Kantar recently presented findings internally to MannKind, which confirmed the company’s belief that Afrezza would be reimbursed at a premium on par with any insulin product, says Edstrom. Mann himself went further, citing discussions from two years ago with “reimbursement gatekeepers from companies that cover around 30% of American lives” indicating that Afrezza, if approved, would command a “five to 10 percent premium” over rapid-acting injectable insulins, and would achieve a Tier 2 placement alongside injectable insulin products within six months.
The perennial concern about any inhaled therapy indicated for a chronic condition like diabetes is what effect it might have on the lungs. Patients taking Pfizer’s failed Exubera product were spooked by lung screenings and a lung cancer warning added to the label, in 2008, after a handful of patients during a post-market study got lung cancer (6 patients out of 4,740, or 0.1%) while using Exubera. Ultimately though, it was the product design and inconvenience of use for patients that probably killed Exubera.
For Afrezza, MannKind has done a formal, two-year study on pulmonary effects, and some patients from earlier clinical studies are still on the drug, and have been for between five and seven years, says Edstrom. Of all of those patients, “we’ve seen really no impact issue in laboratory studies, in any of the clinical trials, or in animal studies,” says Mann, adding that Afrezza “is not in the lungs very long, we go quickly through the membrane into the blood, with no accumulation.”
Despite Mann’s persistence and undying enthusiasm for Afrezza, he’s something of a bull in a bear cave, with respect to inhaled insulin. Nothing shows confidence more than putting your own money at stake, but there’s no successful product forebear to offer guidance, despite a consistent interest in non-needle insulin delivery going back decades. But Afrezza comes with some very novel attributes, not least of which being an improvement on hyperglycemic events, and a convenience factor for patients who’d rather not inject themselves in public before meals. If Afrezza does win approval, in Western markets and in Asian markets like China, where the population count of adults with diabetes was recently tallied at 114 million, MannKind could potentially end up with the blockbuster drug a lot of people thought it had five years ago.
For a more in-depth and historical look at the company and its founder, see PharmExec’s 2009 feature, The Fate of MannKind.