Upping the Antisense Ante (1991)

Sometime this year, if all goes as expected, at least two biotechnology companies will ask the Food and Drug Administration for permission to begin human testing of their experimental drugs aimed at cancer and AIDS. The problem is, FDA isn't sure how to evaluate the strange compounds. So novel are these drugs, made of chemically modified DNA, that the federal agency can't decide how to classify them. Are they biologicals or drugs? asks one FDA spokesman rhetorically, referring to the agency's traditional distinction between naturally occurring compounds and synthetic ones. I'd say the question hasn't been fully resolved yet. The source of the confusion is a designer-drug technology called aptly enough antisense. This relatively young science gained some media attention a few years ago as it became popular among a handful of basic researchers (SN: 6/10/89, p.360). Recently, however, antisense has blossomed into a highstakes, big-bucks specialty, envisioned by its supporters as a revolutionizing force in clinical pharmacology The once obscure field now boasts its own peer-reviewed scientific journal ANTISENSE RESEARCH AND DEVELOPMENT and has spawned nearly a dozen new biotechnology companies. Many of these already have struck multimillion-dollar agreements with huge pharmaceutical manufacturers, which hope to commercialize the products now speeding down the pipelines of the small start-up companies. Almost giddy with promising results from test-tube studies and a few animal tests, researchers wax eloquent about a new era of DNA-based drug design in which a host of diseases will fall prey to the antisense approach. The potential market for antisense drugs is huge, they gush -about $25 billion by 1992, according to some company estimates. But despite all the ballyhoo and venture capital madness, substantial barriers stand between antisense investors and their drug-induced dreams. Researchers know little about the potential toxicity of their custom-designed DNA strands. And the art of targeting these compounds to their destinations diseased tissues and cells, and the appropriate compartments within cells remains in its infancy Meanwhile, high manufacturing costs and difficulties in making commercial quantities of antisense strands still hamper thorough studies of these drugs in laboratory animals. Moreover, scientists suspect that the incredible specificity of the new drugs may make animal models poor predictors of safety and efficacy in humans. Indeed, although some animal studies are underway, company representatives suggest that the extensive animal testing typically required before human trials of new drugs may be inappropriate for this unique pharmacological product. But with FDA confessing its broad unfamiliarity with antisense science, waivers may prove difficult to obtain. Researchers concede that, depending on how things go, five years or more may pass before final FDA approval of the first antisense drug. However, they add, with traditional pharmacological agents remaining largely ineffective against many cancers, viruses and chronic ailments and with more than $100 million already invested in experimental antisense therapeutics the field deserves rapid regulatory attention. Says Nigel L. Webb, chairman and chief executive officer of Hybridon, Inc., an antisense company in Worcester, Mass.: I submit this may be the time to educate FDA about what antisense is.