San Francisco Chronicle
Monday, March 5, 2001
Ronald Rosenberg, Boston Globe
The pill you swallow must navigate its way through your stomach before it passes into the bloodstream, with just a fraction of its medication intact.
By contrast, injectable drugs often get to the right place at nearly full strength. But they're not as convenient as swallowing a pill -- and they hurt.
So pharmaceutical companies and their partners are looking for alternative ways to deliver prescription drugs. One is to inhale medications, as asthma sufferers have long done.
Nearly a dozen drug companies are developing inhaled versions of, and breathing devices for, drugs patients now take by needle. These include the painkiller morphine, the drug Avonex for multiple sclerosis, cystic fibrosis medications and some osteoporosis drugs for women.
But the inhaled drug closest to gaining U.S. Food and Drug Administration approval is insulin, where a single huff could replace a premeal injection.
"With pills, you sometimes are fighting Mother Nature," said Robert Chess, chairman of Inhale Therapeutic Systems Inc. "We saw that an inhaled drug, one that could go deep into the lung and move quickly into the bloodstream, was the way to go."
Chess said the goal is to create medications in a powder form "that you could take in the summer at a ballgame in Fenway Park" -- something you can't do with injectable insulin."
His San Carlos company is a pioneer in inhaled therapeutics. It is working with Pfizer Inc. to develop the first inhaled insulin product, which both companies hope to have approved by the FDA next year.
Inhaled insulin is intended initially for Type 1 diabetics, whose bodies produce no insulin. They depend on insulin injections before each meal and often at bedtime. They represent about 10 percent of the estimated 16 million people with diabetes in the United States.
Last month, Pfizer's Phase II results, reported in the British medical journal Lancet, showed that inhaling insulin before meals can replace an injection of the drug. The results were encouraging to companies seeking substitutes for the three to four daily insulin injections.
Aradigm Corp. of Hayward, meanwhile, has developed an electromechanical device that can tailor insulin doses, prevent overdoses and keep track of usage.
Alkermes Inc., of Cambridge, Mass., has developed a simple inhaler device packaged with insulin particles the size of circuits in computer chips. Even at that microscopic size, diabetics who breathe in insulin will wind up with only 10 to 13 percent of the drug reaching deep into their lungs. Alkermes chief executive Richard Pops and others say that is equal to the amount of insulin in the injectable form.
But some physicians question the long-term effects of inhaling drugs such as insulin. They are skeptical that inhaled drugs will ever replace injectable medication.
"Despite its many inconveniences, injected insulin is an old friend," Dr. David Nathan, a diabetes specialist at Massachusetts General Hospital, wrote last month in the Annals of Internal Medicine, a publication of the American College of Physicians and Surgeons.
"Without a clear appreciation of the long-term effects of (inhaled) insulin in the lungs, we may be exchanging the inconvenience of injections for new complications of diabetes therapy."
In January, some Wall Street analysts lowered their earnings estimates for Inhale Therapeutics Systems for the same reason -- potential long-term safety concerns.
Still, other drug companies are exploring ways of creating inhaled versions of other well-known injectable drugs. Inhale is also working with Biogen Inc. to develop an inhaled version of Avonex, the leading multiple sclerosis drug.
Moreover, Chess said his company is working with Eli Lilly & Co. on a new drug, called Forteo, for women with osteoporosis. The drug aids in bone growth and is being tested in both inhaled and injectable versions.
Aradigm, for its part, is working with Novo/Nordisk SA, the European pharmaceutical-maker, on inhaled insulin.
Aradigm is also developing inhaled morphine with Glaxo-SmithKline to treat severe pain. Both companies plan to begin a Phase III pivotal trial of inhaled morphine later this year. It is among seven drugs the company is developing.
"We think (that)
after injectables, we can go after pills, because oral delivery of medicines
is rather slow," Aradigm Chairman Richard P. Thompson said.
©2001 San Francisco