Never mind, Exubera. Pass the… inhaled insulin thing. Alfred Mann is so certain he can succeed where Pfizer failed that he’s betting nearly $1 billion of his own money to develop an alternative to the ridiculed device. The 82-year-old ceo and controlling shareholder in MannKind tells The New York Times that his inhalable insulin isn’t just a way to avoid needles, but is medically superior.

“I believe this is one of the most valuable products in history in the drug industry, and I’m willing to back it up with my estate,” he tells the paper during an interview in his 23,000-square-foot mansion overlooking the San Fernando Valley in California on a recent Saturday evening, which he says was the only opening in his seven-day work schedule.

Despite his remarkable entrepreneurial career - the Times notes that Mann has founded more than a dozen aerospace and medical device companies - some wonder whether he has so much invested in this latest effort, both financially and emotionally, that he can’t see any odds against him. “I don’t know of an individual who has spent as much of a personal fortune on a long shot,” Andrew Forman, an analyst with WR Hambrecht, tells the paper. He adds that MannKind faces numerous regulatory and patent challenges, as well as competition from Eli Lilly and Novo Nordisk.

The talley to date - Mann has invested $566 million in MannKind and owns just under half the company. He has also agreed to lend it an additional $350 million. The total of $916 million represents a “big part” of his estate, he tells the Times, while declining to comment on an estimate by Forbes that he is worth $2.2 billion. This much money would cause just about anyone to inhale, yes?

The money was necessary to keep the company afloat, the Times writes. MannKind, which has spent about more than $700 million on its insulin, has attracted some prominent investors, like Legg Mason’s marquee stock picker, Bill Miller. But it has faced skepticism from many other investors and has not yet attracted a big pharmaceutical company to market its drug and to help defray development costs.

Still, some experts say there is promise in MannKind’s product, Technosphere Insulin. “It is different from anything we have now, and it’s different from any of the other inhaled insulins,” Irl B. Hirsch, a professor of medicine at the University of Washington who tells the paper he consulted for MannKind but donated his pay to charity. And he believes Technosphere had the best chance of succeeding compared with other insulin inhalers.

Mann, the son of a grocer, studied physics at the University of California, Los Angeles, but quit before getting a doctorate so that he could take a job to support his wife at the time and their child. One of his early successes was Pacesetter Systems, a heart pacemaker company he started around 1970 and sold to Siemens for $150 million in 1985. Then came Minimed, a maker of insulin pumps for diabetics, which was sold to Medtronic for about $3 billion in 2001. Three years later he sold Advanced Bionics, a maker of implants that allow deaf people to hear, to Boston Scientific for $740 million and possible future payments. Then he got back much of Advanced Bionics after a nasty legal fight with Boston Scientific.

MannKind is now in the final stage of clinical trials for Technosphere Insulin and Mann says the company will be ready by the end of next year to apply for federal approval to sell the drug for Type 1 diabetes, which often starts in childhood, and the far more prevalent Type 2, which often occurs at older ages. Controlling blood sugar, or glucose, by using insulin or other drugs helps diabetics avoid complications like cardiovascular problems and blindness.

The distinguishing feature of Technosphere Insulin is that it goes to work faster than any other insulin on the market, even so-called fast-acting injected insulins. That could be better at helping control the spike in blood sugar levels that occurs after a meal. Technosphere Insulin also finishes its work of helping the body use glucose in two or three hours, faster than other products. That might reduce the risk of dangerously low glucose levels several hours after a meal - a big concern for diabetics.

“That it is inhaled is incidental to the very rapid onset of its action and the short duration of its action,” Jay Skyler, a diabetes expert at the University of Miami, who has bought stock in MannKind, tells the paper.

The International Diabetes Federation issued guidelines in September urging better control of glucose spikes after meals, saying there was evidence they could contribute to complications of diabetes even if average blood sugar levels were kept in control. But there is disagreement, and some studies have not shown a risk from such spikes. David Nathan, director of the diabetes center at Massachusetts General Hospital, contends that the new emphasis on glucose spikes after meals was “all marketing talk” by companies developing fast-acting drugs.

In any case, MannKind has yet to show its insulin is better than others, and there is some suggestion it might even be too short-acting. In clinical trials it has lowered average glucose less than a fast-acting injected insulin, though the differences were not statistically significant. Moreover, many more patients on Technosphere than the injected insulin discontinued treatment, for reasons not fully clear.

The former chief medical officer of MannKind, Dr. Wayman Wendell Cheatham, filed a wrongful-termination lawsuit in 2005, accusing MannKind of hiding information about the drug’s formulation from the FDA. MannKind denied that and countersued for libel. The case was settled in June on undisclosed terms.

Analysts say there were several reasons Pfizer’s product, called Exubera, failed, including missteps by the company and the fact that injections hurt less than they once did because needles are thinner now. Critics said the Exubera inhaler, about the size of a tennis ball can, was cumbersome. Insurers balked at paying higher prices for a product that offered no medical advantage over injected drugs. And Exubera caused a slight decline in lung function.

Mann says Exubera was “an expensive way to fairly inconveniently deliver insulin in a manner which has no clinical advantage.” MannKind’s inhaler is only slightly larger than a cellphone. The company says its product has not caused lung problems, although longer testing is needed to prove that. The F.D.A. might require lung testing for patients using any inhaled insulin, just as it did for Exubera.

Both Eli Lilly and Novo Nordisk are also in late-stage testing of inhaled insulin products. And Nektar Therapeutics, which licensed Exubera to Pfizer, is now looking for a new partner in an effort to keep the product on the market. Nektar, which says it has received e-mail messages from patients desperate to keep using Exubera, has been developing a smaller, improved inhaler.

Another uncertainty is Mann’s age. “If something were to happen to him, you wouldn’t have that pot of money to reach into all the time,” Solomon Steiner, who helped invent Technosphere technology and started a company in 1991 to develop it, tells the Times.

When that company, Pharmaceutical Discovery, ran out of money around 1997, Steiner persuaded Mann to invest. In 2001, Mann merged the company with two others he controlled and named the new entity MannKind, a decision Steiner questions. “Once you put your name on it, how can you let it fail?” says Steiner, who left MannKind in 2003, apparently after some disagreements with his new boss. He now runs a potential competitor, Biodel, a company developing a rapid-acting injected insulin.

Mann, who survived two minor bouts of cancer but says he is now healthy, said his will instructed the foundation that is to inherit his wealth to make sure that his companies have enough money. And he says the company’s name was meant to be a joke.

It may be for the best that he is putting his money into diabetes because Mann has had some trouble giving it away. About a decade ago he said he would give $100 million each to up to 12 universities to establish institutes to help turn faculty ideas into marketable medical devices. But only three institutes have been set up so far, in part because some schools feared losing control of faculty inventions.

As for his six biological children, Mann says he had already given them more than he should have, turning them into idle multimillionaires. (He has also adopted the daughter of his current wife, his fourth). “One tried working for three days and didn’t like it,” he says. “Another didn’t work a day in his life,” and adds that “I would feel more comfortable if my kids were doing something worthwhile.”

He controls eight other companies working on various devices, like one that would allow the blind to see and another that would treat ringing in the ears. “I feel I’m blessed with some ability and resources that enable me to tackle these issues,” he says.

Source: The New York Times