Amylin Pharmaceuticals Inc. presented human clinical data showing itsjuvenile-onset (Type I) diabetes drug, tripro-amylin, can improve post-meal glucose control. However, the San Diego company also said thatPhase II studies showed the drug did not measurably alter thehypoglycemia induced by experimental insulin overdose as comparedto placebo.Amylin presented the data Sunday at a company-sponsored symposiumin conjunction with the annual meeting of the American DiabetesAssociation in New Orleans. It was a double-blind, placebo-controlledstudy in which patients with juvenile-onset diabetes continued theirusual insulin therapy, and self-injected tripro-amylin three times a dayfor 14 days. Dose levels were 30, 100 and 300 micrograms.The mixed message resulted in Amylin (NASDAQ: AMLN) stockfalling 33 percent, down $3.75 to close at $7.50 Monday in trading of816,660 shares. David Webber, an analyst with Alex. Brown & SonsInc., downgraded the stock from "buy" to "hold.""This is a market that reacts very strongly to anything less than purelypositive news," Webber told BioWorld. "One major hypothesis thathad been presented to investors to explain the role of amylin in ahealthy person was its role in modulating the effect of insulin so as toavoid hypoglycemia (dangerously low blood glucose levels)."The company's news "suggested to me that the molecule is not fullyunderstood," Webber said. "That increases the risk in the product andin the stock."Richard Krawiec, director of corporate communications for Amylin,painted a positive picture of the results presented Sunday."The important news there is self-injected tripro-amylin improvedglucose control in diabetic patients after meals," Krawiec toldBioWorld. "At the lowest doses tested, we not only saw that the drugwas well-tolerated, but that it produced peak blood levels of tripro-amylin in diabetic patients which were consistent with the range ofamylin levels found in normal individuals."Very clearly we could see the difference in the glucose response aftermeals," he said. "We think we've shown a medically relevant effecthere, one that gives us clear-cut endpoints for Phase III" studies, whichhe said are expected to begin in the latter half of 1995.The company plans to continue its Phase II program with additionalstudies looking further at dose refinement, mechanisms of action andpreliminary efficacy of the drug. Amylin said that 100 microgramslikely would be the highest dose level _ 20 of 21 patients taking 300micrograms reported gastrointestinal symptoms, and eight withdrew _and that doses less than 30 micrograms would be tested.The drug, also known as AC137, is a modified form of the pancreatichormone amylin, and used as an amylin restoration therapy. Peoplewith Type I diabetes are deficient in amylin, as well as insulin, andsuffer swings in blood glucose.While the approach to treating Type I diabetics involves replacingamylin, the approach to treating Type II (adult onset) diabetes involvesblocking excess amylin activity. Toward that end, Amylin and GlaxoInc. have a collaboration dating back to 1991.In addition to its Phase II announcements on Sunday, Amylin reportedthat Glaxo, of Research Triangle Park, N.C., has begun Phase I humanpharmacology studies of amylin blocker GG747 (or AC253). Glaxoplans to evaluate the compound's effect on oral glucose tolerance andon insulin sensitivity as precursors to studying it for Type II diabetes.Glaxo already has completed a dose-escalating, safety and tolerabilitystudy with GG747 in healthy humans in the U.K. Studies of thatcompound are complementary to those involving another peptideantagonist, AC625, which is being tested in a Phase I trial that startedin April.The AC625 trial is preparatory to investigating its ability to inhibitamylin-evoked increases in blood renin and its potential to reduceblood pressure and improve the metabolic status of patients withinsulin resistance syndrome, said Timothy Rink, Amylin's presidentand chief technical officer. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.