Is The 21st Century Cures Act Good Or Bad For The Biopharmaceutical Industry?

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Ordinarily, I differ with Harvard Medical School’s Dr. Jerry Avorn on healthcare issues, particularly when it comes to his views on the pharmaceutical industry. For example, we are on opposite sides of the spectrum when it comes to the importance of the interaction of physicians with drug representatives as well as on the pricing of new medicines. However, the recent perspective that he co-authored with Harvard colleague Dr. Aaron Kesselheim in the New England Journal of Medicine entitled “The 21st Century Cures Act – Will It Take Us Back In Time?” raises a number of valid concerns.

The purpose of this Act, recently introduced into Congress, is to promote the development and hasten the approval of new drugs and devices. There are some good parts to it. For one thing, it provides for an annual 3% increases in the NIH budget, which has been stagnant for the past few years and which desperately needs more funding to capitalize on emerging scientific insights.  It also calls for the creation of an “Innovation Fund” for the NIH to the tune of $2 billion per year for 5 years to stimulate further growth. The bill also dictates that the FDA consider non-traditional clinical trial study designs to speed the approval of new drugs. These changes would be welcome.

But Avorn and Kesselheim feel that the Act goes too far in pushing the FDA to speed the drug approval process:

An underlying premise of the bill is the need to accelerate approval for new products, but this process is already quite efficient. A third of new drugs are currently approved on the basis of a single pivotal trial; the median size for all pivotal trials is just 760 patients. More than two-thirds of new drugs are approved on the basis of studies lasting 6 months or less – a potential problem for medications designed to be for a lifetime. Once the FDA starts its review, it approves new medications about as quickly as any regulatory agency in the world, evaluating nearly all drug applications within 6 to 10 months, an impressive turnaround for such complex assessments.

 

These are fair points. The authors then go on to raise issues around the bill’s encouragement of the FDA to approve drugs based on a drug’s impact on biomarkers or other disease surrogates, rather than actual clinical trials that assess the efficacy of the drug in halting or reversing a disease. This is indeed concerning. Studies have shown that just because a drug shrinks a tumor doesn’t mean it enhances survival. While a drug might stabilize bone formation, it may not prevent bone fractures. Even the much hallowed biomarker for heart disease, LDL cholesterol, is not without issues. The CETP class of lipid modulators, while designed to raise a supposedly protective biomarker, HDL cholesterol, are also potent LDL lowering agents. However, the first CETP Inhibitor, Pfizer’s torcetrapib, despite profoundly remodeling heart patients’ lipid levels for the better, failed in late stage clinical trials due to an increase in all-cause mortality. Clearly, it would have been a mistake for the FDA to approve this drug on the basis of biomarkers alone. In fact, Merck is now conducting long-term outcome studies with its CETP inhibitor anacetrapib, to prove its value to regulatory agencies.

Congress is undoubtedly attempting to placate patient advocacy groups with the 21st Century Cures Act. Patients and their families are often desperate for new medicine when available drugs fail. When there are new drugs in the pipeline that might benefit patients who have exhausted all other possibilities, they want the FDA to provide access and not to require more tests. But often these clinical trials are necessary to understand the risk-benefit profile of the exploratory medicine and to protect a patient’s safety.

So, is it really a problem if patients get access to new drugs sooner, drugs that were approved solely on biomarkers or disease surrogates? Yes, because if such a process is instituted, patients inevitably will be exposed to a drug that, after long-term usage, will have unforeseen damaging effects. No drug is without side effects. Who will be blamed for this? Certainly not the Congress. In fact, one can envision that certain politicians will capitalize on such an event by saying that the biopharmaceutical industry has far too much influence on the FDA. Once again, the biopharmaceutical industry will have to deal with a blow to its reputation at a time when the industry is trying to restore its good name.

The industry might benefit in the short-term by the more rapid approval of experimental medicines. However, the downstream consequences may outweigh any immediate benefits. Avorn and Kesselheim are correct when they say “political forces…could lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit.”

Source: Forbes