A vigorous competition is now under way to develop a new class of gene therapies and genetically engineered drugs that hold great promise for treating heart disease. The treatments trigger the growth of new blood vessels in the heart, providing a detour around clogged arteries. Indeed, early results suggest that so-called angiogenesis drugs might one day become an important alternative to the 500,000 bypass operations and 400,000 angioplasties performed in the U.S. every year.
Lately, however, researchers seem to be offering more hype than help. At the annual conference of the American College of Cardiology from Mar. 12-15 in Anaheim, Calif., researchers distorted and inflated test results that were, at best, inconclusive. That's unfortunate. The payoff from the new treatments is likely to be high, but progress depends on sober assessment of new results--not clumsy spin control.
Consider Chiron Corp.'s report in Anaheim on Mar. 12. After small tests showed promise, the Emery-ville (Calif.) biotech company launched a study of 337 patients to see whether a naturally occurring substance called fibroblast growth factor-2 (FGF-2) would boost the time heart patients could exercise on a treadmill, a key measure of heart health. It was the largest and most important test of an angiogenesis drug yet.
The study was a failure. After three months, researchers found no significant difference between the exercise tolerance of patients and an untreated control group. Did Chiron admit defeat? Not quite. After conceding that the study didn't meet its "primary efficacy objective," Chiron's press release saw only sunny skies. "We are encouraged by the positive trends relating to reduction in angina frequency" (chest pain), said Chiron's chief scientific officer, Dr. Lewis T. Williams. One of the study's co-directors, Dr. Michael Simons of Beth Israel Deaconess Medical Center in Boston, said, "Seeing the favorable trends recorded independently by patients and doctors increases our optimism."
Watch out for "trends." It's a code word that means the results were so modest they could have been due to chance--they were not statistically significant. Trends may offer intriguing hints for further study, but they don't prove anything. Yet Chiron denied that it was overselling its study. "It would be inappropriate to characterize it any differently," said spokeswoman Julianna R. Wood.
Investors were hardly fooled. Chiron's stock sank 25%, to 45 3/4 a share, the day after the announcement and closed at 40 5/16 on Mar. 21.
Chiron wasn't alone in its bullish approach. Dr. Jeffrey M. Isner and his colleagues at St. Elizabeth's Medical Center of Boston reported success with gene therapy using a syringe to inject a gene for vascular endothelial growth factor-2, or VEGF-2, directly into the hearts of 30 patients. Twenty-one of them reported reduction in chest pain. Exercise tolerance also improved.
NO CONTROLS. That sounds encouraging, but Isner didn't compare the patients with a control group. There is a good reason: Control patients would have had to undergo so-called "sham" chest surgery without any benefit. But the lack of controls makes the study difficult to evaluate. Some patients, for example, might have improved without the treatment.
Isner acknowledges the shortcoming but says early studies like this one are aimed only at showing safety and establishing proper doses and delivery methods. "It's a fair point that a placebo-controlled trial gives you the most definitive answer," he says. Adding to the confusion, the Food & Drug Administration halted Isner's research a few weeks ago as part of a nationwide review after the death of a gene-therapy patient last September at the University of Pennsylvania. The FDA says it needs more data before Isner can continue.
The agency's questions shouldn't obscure the promise of these new heart-disease treatments. Angiogenesis research continues to generate excitement. But progress depends on careful, controlled studies and unbiased interpretations of the results. What's called for is clarity--not confusion.