INHALE, DON'T INJECT
A new delivery system for drugs holds huge promise
businessweek.com
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.
By Catherine Arnst in New York |
