Inhaled insulin flops, but field may hold promise

Inhaled insulin may be a debacle that pharmaceutical companies want to put behind them as quickly as possible, but many companies are still working to develop drugs that are delivered through the lungs.

Asthma has been treated with inhalants for decades, and inhaled drugs now under development include treatments for other pulmonary diseases, like cystic fibrosis or infections of the lung, as well as a faster-onset version of an existing migraine drug.

“This is a way to deliver high concentrations of medication to the target organ,” said Kevin Corkery, senior director of the pulmonary business unit at Nektar Therapeutics, which last week abandoned its Exubera inhalable insulin program after onetime partner Pfizer Inc said clinical trials found increased cases of lung cancer.

Nektar, known before 2003 as Inhale Therapeutic Systems, is developing inhalable dry powder versions of anti-infectives for treating pneumonia in the lung as well as aerosolized forms of antibiotics for patients with cystic fibrosis, a genetic disease in which the body produces a thicker-than-normal mucus that clogs the lungs and other organs.

Pfizer had already decided last year to stop marketing Exubera, which had only marginal sales despite the pitch of being more convenient than traditional insulin injections. The decision cost the company a $2.8 billion pretax charge.

After the world’s largest drugmaker acknowledged its product was never going to see the blockbuster sales it once hoped, Eli Lilly and Novo Nordisk this year also ended inhaled insulin development programs.

Tiny MannKind Corp remains a notable holdout, repeating this week that it remains committed to its experimental inhaled insulin, Technosphere, which it believes holds advantages over the other products.

“The safety issues related to inhaled insulin really center on the fact that it is a growth factor going into the lung,” said Tim Nelson, chief executive at MAP Pharmaceuticals Inc, which is developing an inhalable migraine drug and an asthma drug for toddlers and preschoolers.

Insulin and related substances called insulin-like growth factors have been shown to increase the risk of developing cancer.

IMPAIRED LUNG FUNCTION

In addition, Exubera has always been associated with slight impairment of lung function, requiring physicians to carefully screen and monitor patients for lung disease like asthma and emphysema.

Nelson said MAP’s products do not hold that kind of risk.

The company expects results late this year from a pivotal-stage trial of a low-dose aerosol form of a steroid used to treat asthma in children too young to use inhalers.

Nelson said MAP’s technology will deliver about half as much steroid to children under age 5 in three to four minutes, compared with the 10- to 15-minute process they are now subject to.

The active ingredient in MAP’s migraine drug, known as MAP0004, is dihydroergotamine, which has been used intravenously for 60 years by hospitals for treating severe migraines. The IV infusion can cause nausea and cardiovascular problems, but MAP’s inhaled drug is not associated with those side effects, Nelson said.

He also said MAP0004 works to calm migraine pain in as fast as 10 minutes, compared with 45 minutes to two hours for commonly-prescribed migraine pills.

“We’re treating migraine upstream ... there is a much broader spectrum of efficacy,” Nelson said.

The first Phase III results from the company’s migraine program are also expected in late 2008.

Morgan Stanley has estimated peak annual sales for MAP0004 of around $250 million and said UDB could see sales of $500 million a year.

Corkery said Nektar and partner Bayer AG are talking with U.S. regulators about the design of a Phase 3 trial of its aerosolized powder form of the antibiotic amikacin.

The company is also working on an inhaled version of vancomycin for treating antibiotic-resistant, hospital-acquired pneumonia.

Nektar has partnered with Novartis and Bayer, respectively, to develop inhalable dry powder versions of anti-infectives tobramycin and ciprofloxacin for cystic fibrosis patients.

Meanwhile, Gilead Sciences Inc, the world’s second-most highly valued biotech company, is slated to hear in September whether the U.S. Food and Drug Administration will approve its application for cystic fibrosis drug aztreonam lysine for inhalation.

Analysts have estimated that Gilead’s drug will see sales of more than $500 million a year.

By Deena Beasley
LOS ANGELES (Reuters)