Let's get one thing straight right up front: We're not talking about inhaled insulin. Sure, it comes out of an inhaler; yes, you breathe it in; and of course it's absorbed deep in the lungs. But please don't use those two unfortunate words. Inhaled insulin was a misguided idea—an attempt to replace needles and injections with something ostensibly more convenient. When Pfizer actually put that product on the market (the ill-fated Exubera in its giant bong of an inhaler), patients and doctors ignored it in droves. After that, Lilly and Novo Nordisk, big players in diabetes care, promptly folded their fast-acting inhaled insulin programs as well. No better than injected insulin, not all that convenient, and potentially dangerous. That was inhaled insulin.
Of course, if you could develop an insulin that worked better than injectable and was just as safe—and it just happened to be delivered by inhalation—that would be a completely different story. Wouldn't it? Patients and doctors would say, "That's different from Exubera." And they'd turn this drug—let's call it Afresa—into a blockbuster.
At least, that's what Al Mann is betting. And a hell of a bet it is. Mann, the legendary 82-year-old serial entrepreneur behind Afresa (also known as Technosphere insulin (TI)) has sunk $919 million of his own money into the project, and has signed a commitment to lend MannKind Corporation, his latest entrepreneurial venture, an additional $350 million to see Afresa through to market. MannKind filed Afresa's new drug application with FDA in mid-March, and though Mann and company are confident, the drug still has to clear some daunting hurdles. Will FDA approve another inhaled insulin in this safety-obsessed political climate, especially after the Exubera disaster? Will the agency weigh Afresa's label down with warnings that have less to do with MannKind's drug and more to do with Pfizer's? Will MannKind be able to find a partner that can set aside memories of the most dismal pharmaceutical launch in recent memory? And will physicians, payers, and patients see past the inhaler and recognize Afresa as an important step forward in diabetes control?The stakes are high. Indeed, you could say they're nothing less than the survival of MannKind.
The Mann From MannKind
Alfred Mann is Hollywood's idea of a scientist—the tinkerer who invents gadgets for fun and turns them into a billion-dollar fortune, all the while thinking nothing of it. With products like solar panels, hearing aids, and pacemakers to his name, Mann has turned himself into an indispensable cog in the machine of American healthcare.
The saga starts in 1956, when the Portland, OR, native—UCLA physics degree in hand—founded his first company, Spectrolab, to produce solar panels for spacecraft. Mann liked what he'd created, and over the years launched numerous other companies built around his inventions, including Heliotek (semiconductors and solar cells), Pacesetter Systems (cardiac pacemakers), and Advanced Bionics (neuroprosthetics). In the process, he became a very rich—in 2008, Forbes estimated his net worth at $1.8 billion, ranking him number 262 on its list of the richest Americans.
Mann also became a force in philanthropy; he first turned to diabetes in 1979, developing an implantable insulin pump. MiniMed (now part of Medtronic), the company he formed around the pump, went on to concentrate in diabetes and microinfusion drug delivery. It was so successful that Mann started exploring other pathways in diabetes care.
In 1997, he was presented with an inhaled insulin product created by a small company called Pharmaceutical Discovery. His MiniMed colleagues thought it could be a breakthrough; Mann wasn't so sure. But Pfizer was experimenting with a puffed product of its own, and Pfizer wasn't stupid. Or so he thought.
What really changed Mann's mind, was a glucose clamp study MiniMed conducted to test the new drug's pharmacokinetics. The conditions were far from perfect—researchers delivered the drug via two-dollar drugstore inhalers—but the results were astonishing. At mealtimes, the body of a normal patient delivers a jolt of insulin to the bloodstream, with the level peaking in about 12 to 14 minutes. A diabetic taking prandial (mealtime) insulin gets a peak in about an hour, regardless of whether the drug is delivered by injection or inhalation. But the drug MiniMed was examining peaked in 12 to 14 minutes, just like the body's own insulin boost. And the bioavailability of the new drug was four times greater than that of the other emerging inhaled insulin products.
"From the beginning, when I saw the kinetics of Afresa and Technosphere insulin [TI], it was clear to me that this was a unique product that would revolutionize diabetes care," says Mann. He bought Pharmaceutical Discovery, folded it in with a couple of his other companies, and MannKind was born.