Two New Drug Treatments Offer Hope to Ulcer Sufferers
Ulcer sufferers, and people with more garden variety heartburn and indigestion, may be able to look forward to two new and interrelated treatments.
But both treatments--a possible new drug for ulcer sufferers and the proposed recasting of an established remedy as an over-the-counter antacid--have raised questions about effectiveness and acceptable balance between risk and benefit.
Omeprazole, the proposed new ulcer drug to be marketed in the United States by Merck Sharp & Dohme under the trade name Losec, would be the first truly new ulcer drug since 1977. According to researchers, it has shown in early tests that it can heal ulcers faster than histamine blockers, which ulcer sufferers have relied on for the last 11 years. But, researchers are cautioning that omeprazole may represent therapeutic overkill for patients with ulcers of average severity because the drug virtually cuts off normal production of stomach acid.
Meanwhile, the makers of two of the best-known histamine blockers--a family of drugs whose most prominent member is cimetidine (brand name Tagamet) --are studying the possible recasting of their products as over-the-counter antacid tablets that would compete with the likes of Tums, Rolaids and Alka-Seltzer.
But researchers involved in tests of chewable or fizzy tablet forms of cimetidine say it may not provide the quick relief demanded by heartburn and indigestion sufferers. Instead, said Dr. Gary Van Deventer, an expert at the Center for Ulcer Research and Education at UCLA and the Wadsworth Veterans Administration Hospital, the new over-the-counter formulations will probably have to be a mix of cimetidine and formulas that are already popular.
Though some researchers say the proposed omeprazole stands to be as dramatic an advance as the histamine-blockers were in their day, its effectiveness may turn out to be as much of a drawback as an advantage. They explain that omeprazole is capable of causing the stomach’s natural secretion of gastrin, the chemical complex that is key to digestive acid function, to almost completely shut off. This unique acid-controlling ability, in turn, stops the chemical action of ulcers, which are small, dime-sized areas of the stomach or intestine in which natural chemical protections fail in the tissue and stomach acid, in effect, digests the stomach or intestine itself.
But a stomach without acid can be dangerously susceptible to disorders ranging from dysentery to cancer, said Van Deventer, who has participated in a number of studies of the drug. Some researchers say the drug’s best use will be in the most severe ulcer cases and in comparatively rare disorders like Zollinger-Ellison syndrome, a type of cancer.
Histamine blockers inhibit acid secretion effectively and induce healing in most ulcers within a few weeks. But omeprazole, which relies on completely different chemistry, induces healing faster and works in situations where cimetidine is partially or completely ineffective.
Yet other researchers worry that omeprazole may be overused by physicians and patients. The alleged overprescribing of Tagamet has been debated for more than six years.
Dr. Malcolm Robinson, an ulcer drug researcher at the Oklahoma City Clinic, is one of a number of experts nationwide who believe that the development of omeprazole represents a major revolution in ulcer therapy.
“I think you can say it is an advance of the same magnitude (as cimetidine),” Robinson said. “Cimetidine represented a quantum leap over what was available before, which was basically nothing but antacids. Omeprazole makes cimetidine look like antacids.”
Robinson’s enthusiasm is not shared by Van Deventer.
“Omeprazole is a lot more effective in terms of turning off acid secretion and it yields higher healing rates,” Van Deventer said, “but the concern is: Do we need anything that much more potent than cimetidine . . . ? Are we going to be trading a higher gain in suppression of acid and a little speedier healing for a bit of a greater risk?”
Ulcers Not Understood
How and why ulcers form is not completely understood. Despite the folk belief that they result from stress or worry, there is some evidence they are genetic in origin, Van Deventer said.
In the normal person, Van Deventer said, acid keeps the stomach essentially free of bacteria. But with acid production turned off, he said, a process can be set in motion in which bacteria colonize, leading to development of a chemical situation conducive--at least in theory--to development of stomach cancer.
There is also a possibility that the acid-secretion effect of omeprazole may make it easier for a person taking the drug to get intestinal disorders ranging from traveler’s diarrhea to cholera. Together, the risks aren’t justified by the benefit of slightly faster, somewhat better healing in the average ulcer patient, Van Deventer said.
Tests comparing omeprazole and cimetidine healing rates have shown omeprazole to have a significant advantage, but many researchers who have confirmed the advantage are not convinced that omeprazole should be used as routine ulcer therapy. Dr. Andre Archambault, of Montreal’s Center of Gastroenterology and Endoscopy, found in a study published earlier this year that omeprazole had better healing rates than cimetidine--at significantly lower doses than the older drug too.
But Archambault said he still does not advocate the drug for all ulcer patients. “It would help in complicated cases and for a severe disease like Zollinger-Ellison,” he said, “But as the first line of treatment for ulcers, I don’t think this (omeprazole) is the true drug that should be prescribed.”
Dr. David Graham, of Houston’s Baylor College of Medicine, agreed: “We can heal ulcers fine now but omeprazole will heal them quicker.”
The Final Tests
Graham said he is about to begin work on what omeprazole’s manufacturers hope will be the last human test before the drug is cleared for marketing as a routine ulcer medication by the U.S. Food and Drug Administration. Graham said 15 investigators around the country are involved. Test results will not be known for at least a year. FDA clearance could not occur before 1990 at the earliest, most experts believe.
Of possibly more immediate impact, said Van Deventer, is work to essentially redesign cimetidine and other histamine-blockers into over-the-counter drugs for the relief of heartburn and indigestion.
(Development of such products is widely believed within the pharmaceutical industry to reflect economic pressures on Smith Kline & French Laboratories, which holds the patent on Tagamet and which has in recent months seen profits slump by more than 25% as sales of prescription forms of Tagamet have fallen. The drug, a company spokesman said, loses its patent protection in 1994 and the firm is hoping to market an over-the-counter product in the early 1990s to capitalize on the remaining term of the patent.) A second histamine-blocker, rantitidine (known as Zantac and licensed to Sandoz Pharmaceuticals Corp.), is also under consideration for over-the-counter sale as an antacid.
Some Testing
Van Deventer said UCLA’s Center for Ulcer Research and Education has been involved in some testing of over-the-counter forms of the drug. One problem, according to Van Deventer and other experts, is that cimetidine has no effect until it is absorbed in the gastrointestinal tract--whereas conventional antacids work immediately by attacking heartburn and other symptoms on tissue linings in the throat, esophagus or stomach.
So an effective product, he said, would probably have to incorporate conventional preparations already on the market with a chewable or fizzy form of cimetidine. Dosage has been a problem, too, said Van Deventer and Robinson. Researchers trying to formulate an over-the-counter product have not succeeded in finding the right effective dose that can work quickly, without side effects.
