After a nearly 80-year hunt to end the need for painful daily injections for diabetics, researchers reported Monday that an experimental oral spray successfully delivers critical insulin into the bloodstream and may spell the end of the needle.
Diabetes is the world's most common metabolic disorder, expected to afflict 300 million people by 2025. As diabetics await the breakthroughs that could cure them, they continue to give themselves shots every day to control their blood sugar levels.
Seven research papers presented Monday at the annual meeting of the American Diabetes Association in Philadelphia showed insulin by mouth had worked exactly as its makers had hoped, with the aerosolized puffs quickly passing through the mucus membranes of the cheeks and entering the bloodstream.
That method is just one contestant in a high-stakes race by drug companies to replace the syringe and tap into a worldwide market estimated at $20 billion annually.
Like most large-molecule pharmaceuticals such as vaccines and hormones, insulin cannot be taken in pill form and swallowed because the digestive tract will break it down and destroy the active elements before they can enter the bloodstream.
Currently, such drugs are administered by injection -- either by a disposable syringe, a pen/cartridge device or an implanted insulin pump. The most common methods involve patients sticking themselves, ranging from once every three days to four or five times daily.
The papers presented Monday at the world's largest diabetes scientific meeting documented the progress of a product called Oralin, made by the Toronto-based Generex Biotechnology Corp., as it wends its way through the regulatory process leading to approval by the U.S. Food and Drug Administration.
Safe and effective
The drug has now passed the first two phases of FDA tests -- indicating generally that it is safe and it works -- and is now ready for wider tests on thousands of patients.
"We have proven that it works, and there were big bugaboos about that," said the primary investigator conducting the Generex clinical trials, Dr. Sherwin Schwartz, director of the Diabetes and Glandular Disease Clinic in San Antonio.
Other experts, fearful of raising false hopes, remained cautiously optimistic.
"One has to reserve judgment until there's independent confirmation, but I must admit the data are impressive," said Dr. Richard Furlanetto, scientific director of the Juvenile Diabetes Research Foundation.
"The nice thing about the aerosol spray would be that patients could dose themselves rapidly. You're having a snack. You can take some extra insulin if you need it. You can take it right before meals or in a restaurant. No need to get out a syringe.
"There is a great need for less invasive and more convenient forms of giving insulin," Furlanetto said. "The easier we doctors can make it, the better our patients can control the disease. And that, of course, leads to fewer complications."
In diabetes, there is too much glucose (sugar) in the blood. Insulin works by stimulating the uptake of glucose into cells and by suppressing the production of glucose by the liver.
People with Type 1 (also called juvenile-onset) diabetes lose their ability to produce any insulin to trigger the conversion of food into energy. About 90 percent of diabetic patients have the much more common Type 2 (or adult-onset) diabetes. They produce enough insulin, but the cells that normally respond to it fail to do so.
Many experts believe up to 25 percent of the diabetic population is needle-phobic and hates the idea of injections. But even for those who tolerate them, the choice between injecting or inhaling would seem obvious. In the U.S. alone, a $3 billion market is at stake.
"It is estimated that 98 percent of all diabetics today are poorly managed. That is a terrible and frightening number," said Anna E. Gluskin, president and chief executive officer of Generex Biotechnology.
"That results in a roller coaster of glucose levels -- sometimes very high, sometimes very low -- that leads to the terrible complications of diabetes -- heart disease, blindness, amputations."
Administered with a pocket-sized nebulizer identical to the ones carried by asthma patients, the insulin oral spray has been shown to cross the buccal membranes of the mouth and deliver the drug to the bloodstream just as a needle does.
"It's extremely fast acting. It gets into the bloodstream in about 10 minutes and reaches a peak in about 30 minutes," said Dr. Arthur Krosnick of the Robert Wood Johnson Medical School in Piscataway, N.J.
In the race to perfect oral insulin, Generex has not been the favorite but has been moving up fast from the outside. Last September, the company, which was formed in Toronto only 21/2 years ago, entered into an agreement with Eli Lilly and Co. to develop this product.
Lilly, a leader in this market ever since insulin was discovered by Canadian researchers in 1921, has been providing Generex with insulin crystals to convert into spray.
The spray is one of a few alternative insulin products that scientists are working on. The one most closely watched has been Pfizer's inhaled insulin powder called Exubera, developed with Inhale Therapeutic Systems Inc., which has completed its clinical trials and is expected to come before the FDA later this year. Novo Nordisk, partnered with Aradigm, has a competing version, which also is absorbed by the lungs.
There is considerable concern about safety for the lungs.
The Oralin spray has completed the second of the three phases of clinical trials necessary before being considered for FDA approval. It now will be tested on large numbers of diabetics to determine if it's safe and effective.
Dr. Louis Philipson, a diabetes expert at the University of Chicago questioned the need for an oral version of insulin.
"I saw 18 patients today, and several of them were on insulin pumps, several were on multiple injections, some were well controlled, some were not," he said. "But of all those patients, only one of them seems desperate to try anything to not take insulin injections. And it's not the injections per se that are driving her nuts. It's that we're having trouble getting her in control.
"To me, this Oralin data is very early data, preliminary data, and it's exciting and may be helpful for a certain minority of patients. Yet I have no problem showing people how easy, painless and convenient it is to take insulin several times a day."
For other opinions, one need only talk to Frank Faso, 10, and his brother Vince, 14, both of whom are in Washington, D.C., this week representing Illinois in the Juvenile Diabetes Research Foundation's Children's Congress 2001. They are telling lawmakers what it's like to live each day with Type 1 diabetes.
The boys, who live in Carpentersville, were diagnosed with diabetes within nine months of each other.
"I have to prick my fingers and test my blood five or six times a day," said Vince. "Then I have to give myself five or six insulin shots -- in my thighs, biceps, stomach. It stinks, but I have to do it. Wouldn't it be cool if I didn't have to keep on sticking needles into myself!"
Frank also must give himself four to six shots every day.
"In my butt, my arms, my stomach. I get through it by forcing my mind to wander and think about other things. Using a spray would mean I wouldn't have to answer people who always are asking, 'does that hurt?'
"Sure, it hurts. But you do it, and get it over with, and get on with your day. But I don't think I'll ever get used to it. I don't think you can ever get used to having to give yourself shots six times a day."