AD Quality Auto 360p 720p 1080p Top articles1/5READ MOREPettersson scores another winner, Canucks beat Kings“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,” Mann said at his 23,000-square-foot mansion overlooking the San Fernando Valley. The interview took place on a Saturday evening, which Mann said was the only chance in his seven-day work schedule. Despite Mann’s remarkable entrepreneurial career – he has founded more than a dozen aerospace and medical-device companies – there are people who wonder whether he has so much invested in this latest effort, both financially and emotionally, that he cannot 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,” said Andrew Forman, an analyst with WR Hambrecht & Co. Forman said MannKind faced numerous regulatory and patent challenges, as well as possible competition from injected-insulin leaders Eli Lilly and Novo Nordisk, which are also developing inhalable products. So far, Mann has invested $566million in MannKind and owns just under half of the company. He has also agreed to lend it an additional $350million. The total of $916million represents a “big part” of his estate, he said, declining to comment on an estimate by Forbes that he is worth $2.2billion. The money was necessary to keep the company afloat. MannKind, which has spent more than $700million on its insulin, has attracted some high-profile investors, including 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. MannKind’s stock, which was above $20 several times in 2006, closed Thursday at $8.66. Pfizer, the world’s biggest drug company, flopped miserably with a seemingly can’t-miss idea. But Alfred E. Mann is so certain he can succeed that he is betting nearly $1billion of his own money on the effort. Pfizer’s failure was a form of insulin that people with diabetes could inhale rather than inject. But last month, after selling only $12million worth of inhaled insulin in the first nine months of the year, Pfizer said it would take a $2.8billion charge and abandon the product. But Mann, the 82-year-old chief executive and controlling shareholder of MannKind Corp., is not deterred. He says his company’s inhalable insulin is a way to avoid needles and is medically superior to Pfizer’s product and to injected insulin. If he is right, he could help change the way diabetes is treated. 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,” said Dr. Irl B. Hirsch, a professor of medicine at the University of Washington who said he had consulted for MannKind but donated his pay to charity. He said that of all the inhaled insulins, Technosphere had the best chance of succeeding. Mann, the son of a grocer, studied physics at UCLA but quit before getting a doctorate so 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 $150million in 1985. Then came Minimed, a maker of insulin pumps for diabetics, which was sold to Medtronic for about $3billion in 2001. Three years later he sold Advanced Bionics, a maker of implants that allow deaf people to hear, to Boston Scientific for $740million plus possible future payments. Then he got much of Advanced Bionics back after a nasty legal fight with Boston Scientific. MannKind, based in Valencia, is in the final stage of clinical trials for Technosphere Insulin. Mann said the company would 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 such as 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,” said Dr. Jay Skyler, a diabetes expert at the University of Miami, who has bought stock in MannKind. The International Diabetes Federation issued guidelines in September urging better control of post-meal glucose spikes, 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 about this, and some studies have not shown a risk from such spikes. Dr. David M. Nathan, director of the diabetes center at Massachusetts General Hospital, contends that the new emphasis on post-meal glucose spikes was “all marketing talk” by companies developing fast-acting drugs. In any case, MannKind has yet to show that 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 formulation of the drug from the Food and Drug Administration. 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 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 said 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 cell phone. The company says its product has not caused lung problems, although longer testing is needed to prove that. The FDA 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 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,” said Solomon Steiner, who helped invent Technosphere technology and started a company in 1991 to develop it. 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?” said 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 said he was healthy, said his will instructed the foundation that will inherit his wealth to make sure that his companies have enough money. And he said 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 $100million 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 said 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,” Mann said. “Another didn’t work a day in his life.” He added, “I would feel more comfortable if my kids were doing something worthwhile.” Mann controls seven other companies working on other devices, such as 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 said. 160Want local news?Sign up for the Localist and stay informed Something went wrong. Please try again.subscribeCongratulations! You’re all set!