Is the Golden Age of drug discovery behind us ?

Interesting article in this months Atlantic Magazine entitled “No Refills”. In the article the author makes the point that today’s FDA probably would not have approved Aspirin or even penicillin, the miracle drug that helped dramatically extend the human lifespan when introduced in the early 1940s. Here is a summary of key points.

IN 2009, ONLY 25 NEW DRUGS WERE APPROVED—LESS THAN HALF THE NUMBER IN THE MID-’90S.
In 1996—arguably the peak of pharmaceutical productivity in the past two decades—the FDA approved 53 NMEs. These days, breaking the 20 mark is rare; last year 19 were approved, plus six “biologics,” substances such as vaccines and antibodies that are based on proteins made by living cells.

• “Blame the FDA,” say conservatives and drug companies. “Blame the companies,” respond liberal activists and good-government types. But as viscerally satisfying as such finger-pointing may be, it offers half-truths at best. For a variety of reasons, we may be entering an age when a miracle cure is just that.

• The number of clinical trials required to support a new-drug application has more than doubled since 1980, while the number of patients needed in each trial has almost tripled. As a result of these and many other factors, the clinical-trial stage now costs more than four times as much, even after adjusting for inflation.

• Making drug trials more expensive can have a big effect on development. Once they’re developed, most drugs are nearly pure profit (a topic of much complaint among consumer activists). The cost is all in the R&D—somewhere between hundreds of millions and nearly $2 billion per drug, depending on which estimate you use. And the single biggest portion of that cost is the very, very expensive clinical trials, in which pharmaceutical companies try to show the FDA that their compound is safe and effective.

• Tougher safety and efficacy standards may also be keeping good drugs out of the public’s hands. Most people agree that today’s FDA would not have approved aspirin; even penicillin, the miracle drug that helped dramatically extend the human lifespan when introduced in the early 1940s, is questionable. Allergic reactions to penicillin kill a higher percentage of its takers than Vioxx ever did, while the gastrointestinal bleeding produced by aspirin means it probably would have flunked while still in animal testing.

• An economist at Tufts who specializes in the pharmaceutical industry, said spending on R&D is 11 times what it was 30 years ago.

• The best-understood diseases already have a lot of good drugs treating them. New treatments need to prove that they have better efficacy, fewer side effects, or something like a longer-lasting dose that makes them superior to the pills already on the market. Longman likens this process to chasing an Olympic sprinter—who has a head start.

• When you’re up against already-state-of- the-art treatments, you’re looking for small improvements. That means you need huge numbers of patients to generate a statistically significant result. And since good treatments already exist, the safety hurdles are also higher—the FDA is less likely to approve a statin that causes internal bleeding than a pancreatic-cancer drug that does the same.

• Drug-plan managers like Medco and Caremark have gotten more aggressive. Drugs that 10 years ago would have been blockbusters—like the anti-platelet drug Effient, Eli Lilly’s answer to Plavix—now face tough scrutiny. In fact, Medco is funding research that it hopes will make the medical case for the continued use of Plavix (which is cheaper) by most patients, while identifying the subset of patients who would benefit from the new drug. That would be great news for health-care costs, but terrible news for Eli Lilly.

The fact is, no single pipeline theory works well on its own; they all interact. A stodgier FDA can mean stuffier decisions inside companies. Smaller pipelines make for bigger mergers. Bigger companies, in turn, may mean smaller pipelines.