An Easy Pill to Swallow

A Jerusalem firm expects its new accordion pill to change the way medicines are administered

Jonathan Liss

Sylvia G. has been suffering from Parkinson's Disease since 1995, the year she turned 70. She took pills for her condition five times a day, till six months ago when her condition deteriorated and it became difficult for her to swallow. Her doctor reduced the total dosage and cut back on the number of times she took pills to twice daily. As a result, however, the deterioration of the nervous system caused by her Parkinson's was likely to accelerate.
Ideally, Sylvia's dosage problem could be solved by giving her time-release pills, which dissolve over time after being swallowed. Pharmaceutical companies have, in fact, designed pills which gradually release their payload over periods of up to 24 hours. But one of the medications Sylvia needs for her Parkinson's, L-Dopa, is only effective if it is delivered to the area at the top of the small intestine just below the stomach known as the narrow absorption window - an area that conventional time-release pills pass through too quickly for the drugs they seek to deliver to be effective. To compensate for too-rapid movement through the narrow absorption window, many drugs that cannot utilize time-release technology are routinely administered in increasingly higher dosages. But this carries the danger of unwanted side effects.
Jerusalem-based Intec Pharma is now developing the "accordion pill" - based on research by Amnon Hoffman and Michael Friedman of the Hebrew University School of Pharmacy - which deals with the problem faced by Sylvia. They suggest that it will revolutionize the way in which an entire class of medicines, those which must be absorbed in the upper small intestine, are administered. If it lives up to the ballyhoo, Sylvia can take her medicine once a day, without having to worry about a short-term overdose or unwanted side effects.
The accordion pill, which starts out at the size of a standard drug capsule, gets its name from the way in which it functions, says Efi Cohen-Arazi, Intec Pharma's new CEO. "On entry into the stomach," he explains, "it unfolds like the flaps of an accordion, gradually releasing its medicinal payload over a period of up to 24 hours." By unfolding to several times its ingested size, the pill becomes too large to fit through the pyloric valve that connects the stomach and duodenum (the upper portion of the small intestine). Trapped near the opening to the lower gastrointestinal tract, the pill releases medication at a consistent rate, assuring continuous absorption.
In addition to maintaining higher dosages of medicine for longer periods of time, Cohen-Arazi says the pill increases the probability that the patient will do what the doctor ordered: "The more times during the day a patient has to swallow a pill, the lower the percentage who can actually keep up with such a program," explains Cohen-Arazi. The accordion pill is a once-a-day solution that solves the patient compliance issue." There's no worry that the patient will be left with a tiny accordion in her stomach; the entire pill - which is a delivery system that can contain any medication - biodegrades and exits the body.
Cohen-Arazi thinks the pill has the potential to revive many pharmaceuticals that failed to make it through the approval processes of the U.S. Food and Drug Administration and other regulatory bodies because of the narrow absorption window problem. "If a pill can't be administered to a patient in healthy dosages, it will never make it past even its preliminary trial stages," he says. "Because the accordion pill bypasses the issue of gastric retention, Intec can go back to the drawing board with many of these 'failed' medicines where other companies left off."
Clinical studies indicate that the accordion pill, which last year got approval from both the U.S. FDA and the European Union's regulatory body, is twice as effective as conventional drug delivery. The idea of a more effective timed-release delivery system, understandably, is intriguing to medical professionals. "Without knowing too much about this [the accordion pill], it sounds very exciting," observes Dr. David Markowitz of Columbia University Medical School in New York. "Conceptually, I could envision multiple therapeutic uses which such a delivery system could provide. In Parkinson's, which includes difficulty swallowing as one of its primary symptoms, a once-daily pill would be of great use."
The "multiple therapeutic uses" Markowitz refers to cover nearly 8 percent of the world pharmaceutical market, including medications for a variety of gastrointestinal disorders, Parkinson's, Alzheimer's, AIDS, and more. This amounts to total annual sales of $30 billion, with the potential for further revenues in the near future.
Other experts take a wait-and-see attitude. "There are too many variables involved to know from the outset that this or that drug delivery system will be effective," says Dr. Lloyd Mayer, of New York's Mount Sinai Medical Center. "Once a drug is released onto the market, everything can, and often does, change." And Alan Greenberg, director of pharmacology at Jerusalem's Shaarei Zedek Hospital, says he'd need more concrete data to evaluate whether the accordion pill has a $30-billion potential - which, he says, would depend on the number of "blockbuster drugs" generating $1 billion or more in annual revenues that it could deliver.
Cohen-Arazi hopes the first accordion pills will roll out of Intec's HQ in Jerusalem and onto the market within two years, but declines to say which specific medicines they will be used to deliver. "We are already in talks with three different internationally recognized pharmaceutical companies," he says, "but I can't say which they are." He will say, however, that he prefers establishing strategic partnerships with different pharmas for different drugs in order to offer the best opportunity "to maximize the uniqueness of what we have."
Cohen-Arazi, who turns 50
in October, was a vice president at California-based Amgen, the world's largest biotech company with annual sales of about $3 billion, before he met Zvi Joseph, Intec's board chairman, through a mutual friend. Joseph, whose previous ventures had been mainly in real estate, began looking for a technology investment in 1999, "before the high-tech bubble blew," as Cohen-Arazi puts it, at a number of Israeli academic research institutions. After purchasing exclusive license rights to the Hoffman-Friedman process through Yissum, the Hebrew University company charged with commercializing scientific discoveries of university staffers, he assembled a group of about 30 private investors, who have so far put a total of $4 million into the project.
Joining Intec realized a long-term goal for Cohen-Arazi. "I always planned on coming back home to Israel. I was only waiting for the right opportunity," he says.
He's now seeking to raise an additional $6-$10 million, for development. "I wouldn't be here if I didn't believe in the potential to become a major player in the international pharmaceutical market," he bubbles, with the enthusiasm of a sales executive. "It is no longer a question if Intec will be successful, only when the success will occur."
In an industry where the odds against bringing out a blockbuster drug or delivery device are 100-1 or more, only time will tell if he's bet on the right pill.

© The Jerusalem Report 1999 - 2004