The Unfilled Promise of Biotech ‘Cures’
When it came to generating innovative drugs, biotechnology’s proud revolutionaries proclaimed that hundreds of cures were just a double helix away. Shelves at the corner pharmacy would groan beneath the weight of new offerings. A 1982 report from Congress’ Office of Technology Assessment asserted that “the immediate direct impact of using genetic manipulation in the (pharmaceutical) industry, measured as sales, can be estimated in the billions of dollars.”
If you look purely at the numbers, the promised embarrassment of riches has yielded more embarrassment than riches. In 1974--the very beginning of genetic engineering--the Food and Drug Administration approved 23 “new chemical entities” (drugs) for therapies. More than 15 technologically tumultuous years later, the FDA last year approved all of 23 new drugs. None were genetically engineered. Of 14 additional “biological” drugs approved in 1990, only one was genetically engineered.
These are hardly the statistics of a revolution.
“The numbers have not increased in a revolutionary way that matches all the rhetoric,” says Dr. Henry I. Miller, director of the FDA’s Office of Biotechnology.
“Without question, there’s not going to be an explosion of new drugs. That’s just not going to happen,” asserts pharmacologist Kenneth Kaitin, the assistant director of the Center for the Study of Drug Development at Boston’s Tufts University.
Why? The answers won’t just be found in the stew of overenthusiastic molecular biologists and media hype. Don’t blame it on the regulators either. What’s happening is a tremendous clash between the economic imperatives of the pharmaceutical marketplace and the chimerical qualities of biotechnology.
Yes, there is a tremendous biotechnology revolution going on--but it is primarily a qualitative revolution, not a quantitative one. Biotechnology has already dramatically transformed the way the Mercks, Hoechsts and Roches of the world design and develop drugs. There is no way to overstate the impact biotechnology now has on the culture of drug design.
“The methodological changes are absolutely breathtaking,” says Carl Djerassi, the Stanford University chemistry professor best known for synthesizing the first oral contraceptive. “But translating these methodologies into actual products takes very much longer.”
Djerassi, who has been actively involved in young California biotech companies, points out that these new biotech methodologies are usually blended with other drug development methodologies so it becomes difficult to measure their direct impact. “To try and relate it to the number of products is nonsense,” says Djerassi, “unless you are also willing to say that the invention of the welding machine is a trillion-dollar business because it spawned changes in the automobile and aerospace industries.”
In other words, biotech is less a “product” than a “process”--and even the experts have confused the two over the last decade. Partly for this reason, there’s less to the FDA numbers than meets the eye. Theoretically, biotech processes could generate thousands of new drugs--but if they are only of marginal medical significance, who cares? By contrast, the right two or three biotechnologically crafted drugs to manage arteriosclerosis, arthritis or colon cancer would make all the difference in the world. In fact, biotech already plays a critical role in shaping the drugs that the FDA now approves. In medicine, qualitative revolutions should matter more than quantitative ones.
Which leads to the other reason why biotechnology hasn’t produced a cornucopia of pharmaceuticals: that’s not what the pharmaceutical houses are gunning for. Tuft’s Center for the Study of Drug Development estimates that a new drug typically costs $231 million and takes 12 years to bring to market. These figures are disputable but, as Djerassi points out, they underscore the reality that “it’s not much more expensive to get approval for a drug that sells hundreds of millions of dollars than tens of millions.”
Consequently, many of the world’s pharmaceutical houses have adopted a Hollywood mentality--go for the “hit,” go for the “blockbuster.” According to the Pharmaceutical Manufacturers Assn., drug companies will spend an estimated 16.9% of their sales on research and development. To recover those costs, these companies aren’t looking to build large portfolios of middle-market drugs, they want to develop the billion-dollar megadrugs that will dominate market share in a huge category--such as Tagamet for ulcers. Biotechnology is thus less of a process to generate lots of product than a methodology to boost the odds of engineering a blockbuster.
While it is true that orphan-drug legislation encourages niche innovation, the fact that it even exists underscores the economic priorities of the industry. Indeed, the smaller pharmaceutical biotech companies have become almost completely dependent upon the giants of the industry to either finance or distribute whatever innovations they have. The numbers that really matter aren’t the quantities of potential new drugs but the amount of financial capital available to see them through the global regulatory approval process.
Now it’s silly to think that the FDA will only be approving between 40 and 50 new drugs a year in perpetuity. That’s just not going to happen. Biotechnology will definitely have an impact on the number of new drugs coming into the marketplace. But those numbers will be measured in increments of dozens, not hundreds.
Ironically, the FDA’s Miller predicted as much nearly a decade ago in an article “Designer Genes for Producing Drugs: Will They Wash?” written for the Journal of the American Medical Assn. He warned that people were being far too optimistic about biotechnology’s short-term potential and impact.
Today, as the man who oversees the FDA’s biotech efforts, Miller notes that the technology is just beginning to have a quantitative impact. “There are now scores of applications for marketing (new drugs) in the pipeline,” he observes. “The number of products that are being considered by our advisory committees has been increasing exponentially each year.”
There are now more than 800 discrete clinical trials under way, says Miller, “about half of them duplicative.” That, he says, is “approximately double what it was five or six years ago.”
That doesn’t mean that all these nascent drugs will come to market or that they will prove to be breakthroughs when and if they arrive. What it does mean is that biotechnology processes are, pun intended, taking on a life of their own.
The implications are clear: We won’t begin to see a panoply of bioengineered drugs until at least the second half of this decade. What’s more, they are likely to be very expensive when they arrive. That, in turn, may lead to pressure to reduce the number of drugs that will be listed on Medicare reimbursement schedules as a way to better cap health care costs.
To put it crudely, biotechnology will ultimately create both a qualitative and quantitative revolution in drug development. But the true impact of that revolution is going to be determined more by basic economics than by applied technology.
