Brandy M. Hacker, a 25-year-old medical worker in Converse, Tex., was diagnosed with diabetes when she was 7. A year ago, she had to give herself four shots of insulin a day to keep the disease at bay. But for the past 12 months, she has been part of a clinical trial of a device made by Inhale Therapeutic Systems that lets her breathe in the insulin she needs before each meal--cutting down her needle time to once a day, right before bed. "I love it," she says of the inhaler. "I can feel the insulin reacting a lot faster, and it's a lot easier to take out before meals than a needle." Other diabetics are "amazed, completely amazed" when she tells them about it, and Hacker says she regularly hands out information on how to get in on the trial.
Such enthusiasm is music to the ears of Inhale Therapeutic Systems, a San Carlos (Calif.) company started eight years ago to focus on the unglamorous world of drug delivery. Inhale is attracting a lot of buzz for its unique device for getting medicine down to the deep lung, where it can be easily absorbed into the blood stream through a single layer of tiny air sacs called the alveoli. Its product is in human trials for use with six drugs, and Inhale has partnerships with such big names as Baxter International, Pfizer, and Eli Lilly.
The device has also attracted the attention of Wall Street. Inhale has yet to report a profit--it lost $9.98 million in 1997 on revenues of $16.2 million--but its market could be huge. Worldwide revenues for insulin, including needles and supplies, are about $3 billion, while the market for all peptide and protein-based drugs, for treating diseases as diverse as female infertility and blood-clot prevention, is $10 billion. At least six analysts are recommending the stock, which climbed from 20 1/4 last August to more than 30 in late January. "It's a good way to play the biotech sector with lower risk," says Prudential Securities Inc. analyst Caroline Copithorne. "I like their strategy of developing delivery technology for drugs that are already available."
The strategy grew out of a realization by Inhale founder John S. Patton while at Genentech Inc. in the mid-1980s: It's one thing to develop an amazing bioengineered drug and quite another to get it into the body. Most bioengineered compounds are made of peptide or protein-based molecules, as is insulin. These molecules are too large to pass through the gut in pill form--the stomach digests them before they reach the bloodstream. Skin patches or nasal inhalers won't work, either, without the help of undesirable enhancers such as detergents or electrical impulses. The skin and nasal membranes were designed to keep large molecules out of the body.
That leaves needles as the most effective delivery method--and the most hated. Study after study shows that 72% to 82% of consumers find needles inconvenient, complicated, and frightening. "There is no question that needle phobia is a major problem with insulin compliance," says Dr. Nancy Y. Bohannon, a medical professor at the University of California at San Francisco.
Drug companies have been trying for decades to come up with an alternative to the needle. But for biotech companies, whose main focus is proteins, the quest has added urgency. Patton, now vice-president for research at Inhale, says that while at Genentech he and other scientists "looked at every orifice" for an entryway to the bloodstream. "When we put [human growth factor] into the deep lung, I couldn't believe the blood levels that came back," says Patton. "I scratched a big star on the data and said `I'm going to start a company."' Three years later, Patton went out on his own.
SINGLE ENTRY. Patton staked his future on the idea that "the deep lung is really the one door that Mother Nature left open." But getting through it is not easy. The airway pipes are covered with a mucus meant to filter out large molecules, while very small molecules are exhaled before they can be absorbed. To reach the deep lung, a drug must be delivered in particles one to three microns in size with slow inhalation.
The metered-dose inhalers used for asthma drugs are not a good option. They use high-pressure propellants to blast the drug into the back of the throat, where it becomes lodged. Only 5% to 10% makes it to the lung--okay for asthma treatments, but a bad ratio for more costly biotech drugs. Plus, it's hard to coordinate breath intake with the pumping action, leading to varying doses. Liquefying the drug won't work because liquid peptides and proteins soon degrade at room temperature.
After three years of work, Inhale came up with a way to turn large molecules into a fine powder without degrading them. The powder is packaged into blister packs inserted into an inhaler about six inches long. Pumping the device forces air into the chamber, breaking open the blister pack and creating a cloud of powder. The patient inhales in one deep breath, receiving the medicine first and then a volume of air that forces the drug deep into the lung.
FREEBIE? Inhale's biggest success is consistency: Several studies have found that the device regularly delivers from 20% to 50% of a drug to the bloodstream. "The classic problem with inhalants is that the results were not reproducible," says Robert S. Langer, professor of chemical engineering at the Massachusetts Institute of Technology. "This Inhale device is really pretty neat." The downside: Inhaling is not as efficient as injecting. "This method is likely to increase the cost because you need to use more of the drug," warns Richard D. DiMarchi, vice-president for research technologies at Eli Lilly & Co. Inhale President Robert B. Chess suggests that the extra drug cost could be offset by eliminating needles, which can only be used once. Chess notes that diabetics spend an average of $260 a year on insulin and $160 on needles. "A drug company may decide to give away our device, sort of like giving away the razor to sell the blades," says Chess.
Lots of companies are interested in the razor. Inhale's development agreements for 10 drugs include two for osteoporosis and one for genetic emphysema. But analysts say the first compound likely to reach the market using Inhale's device is insulin, possibly in two to three years. Pfizer is already in the second phase of trials of inhaled insulin with 240 patients. "It really is going to be a major breakthrough," predicts Dr. Sherwyn Schwartz, director of the Diabetes & Glandular Disease Clinic in San Antonio, a participant in the trial. "I don't see any downside. Everybody loves it." Perhaps love means never having to use a needle.