No one is thrilled with the way new drugs and medical devices come to market in the United States - not the biotech and pharmaceutical companies, not the regulators at the Food and Drug Administration (FDA) or National Institutes of Health (NIH), not physicians, and certainly not patients desperately in need of new therapies.
The process is hugely expensive and incredibly slow. According to the Tuft's Center for the Study of Drug Development, the average cost of bringing a new prescription drug from lab to market now tops $2.5 billion and takes more than 10 years.
That can make for a real thrill ride where investors are concerned, as share price for a pre-profit biotech can rise and fall dramatically and unpredictably with every related data release, financial report, news item, or regulatory hiccup over an entire decade, making long-term investment a crapshoot, at best.
But new regulations on the table could change everything for biotech investors and critically ill patients...
Dying for a Change
The problem: antiquated laws that weren't designed to keep up with the explosion of research and innovation now taking place in medicine.
The challenge: speeding up the development and regulatory process, while continuing to ensure the safety and efficacy of new therapies.
There's also a second challenge of maintaining a robust environment for basic research, usually done by university or government scientists, which leads biotechs to new drug discoveries.
In April, 2014, the Energy and Commerce Committee of the House of Representatives decided to take on that challenge by launching an initiative called 21st Century Cures.
Since then, after more than a dozen roundtables, five whitepapers, and eight hearings, the initiative has produced a piece of legislation, aptly named the 21st Century Cures Act. It's now in its second draft.
This Couldn't Come at a Better Time
The big question, of course, is this: will the Act do what it's intended to do, or will it just cloud the field with empty promises and onerous regulation?
The legislation covers three broad areas: discovery, development, and delivery.
Let's take a look at a few of the provisions included in the current version of the bill.
- Increased funding for the NIH. This would represent a reversal in direction for the NIH, which has seen its budget cut by 25% since 2013. A couple of U.S. Senators, Lindsey Graham (R-S.C.) and Dick Durbin (D-Ill.) are doing something similar in the Senate, but instead of a new bill, they will co-chair a new Senate caucus, which will focus on supporting NIH research. The difficulty here will be in finding a way to come up with the money in a climate of sequestration and budget reduction.
- A new grants program. An "Innovation Fund," will support young, emerging researchers and offer capstone awards to outstanding established scientists, especially in promising new areas of study such as precision (aka personalized) medicine. There is also an offer of student debt forgiveness extended to young scientists who agree to work as researchers for the NIH.
- A global pediatric clinical trials research network. Establishing this network would require working closely with regulatory agencies in other parts of the world, such as the European Medicines Agency (EMA). This may be trickier than it sounds. Although the FDA and EMA would seem like similar entities at first glance, there are significant differences between them. For example, although both agencies evaluate the safety and effectiveness of new drugs, the FDA also issues marketing approvals, while the EMA leaves those decisions to the European Commission (EC). The obstacles aren't insurmountable, but they're far from easy.
- Increased availability of data. Study results from NIH funded research will become standardized and made widely available. This is an excellent provision and will help prevent redundant research, which can end up wasting millions of dollars.
- Council for 21st Century Cures. This nonprofit public-private corporation will have a mission to facilitate the discovery, development, and delivery of innovative cures, treatments, and preventive measures for patients by fostering collaboration. Since the board will include representatives from the FDA, NIH, patient advocacy organizations, and life sciences industry, we have to assume the "cooperation" will be among those groups.
- Patient-focused drug development. This will add a new wrinkle to the drug development process: it will take into account patients' reported experience with new drugs, which can then be incorporated into the FDA's risk/benefit analysis. The FDA, with support from patient groups, has long wanted to add something like this to their review process, but it's unclear how the additional information will make the process faster or more efficient.
- Establishing rules for identifying and qualifying biomarkers. This is similar to a program the FDA already has. There is also a call for a new accelerated approval development plan that accepts biomarkers as surrogate endpoints. Biomarkers are measurable medical signs, such as pulse rate or blood glucose level, that indicate certain processes, such as disease, are going on in the body. Sometimes they can accurately predict the clinical outcome of those processes and are used as "surrogate" endpoints in clinical trials for serious, life-threatening diseases such as cancer or heart disease. For example, reduced cholesterol is sometimes used instead of reduced mortality as an endpoint in studies looking at heart disease, because waiting to actually demonstrate that people lived longer could take many years and keep a new, effective drug off the market for no good reason.
Under the new provision, use of biomarkers as endpoints would extend to use in any patient population where dependable biomarkers can be established, and used as the basis for accelerated approval. Currently, this is only allowed in treatment studies of serious, life-threatening diseases.
Developing rules for identifying these biomarkers is a laudable goal, but in the past, has proven devilishly difficult. Reversing tumor growth, for example, may seem like a great success, but in some cancers, it doesn't predict overall survival.
Some other provisions of the bill include a mandate for the FDA to establish guidance for precision (personalized) medicine drugs; a call to use physicians' clinical experience in support of drug trials for safety and efficacy, especially for post-approval monitoring; help for patients in getting experimental drugs for compassionate use; expedited development of antibacterials for specifically defined populations; the establishment of breakthrough and priority review designations for medical devices; and FDA regulation of medical, but not health, software as a medical device.
Biotechs Could Still Miss Out on the Act
While there seems to be plenty of support for basic research in the bill, and nods are given to patient groups and practicing physicians, what is missing, unfortunately, are substantial benefits for the biotechs that actually develop new drugs.
The original draft of the legislation contained offers of increased market exclusivity for new drugs and biologics, which pricked up the ears of the bioscience industry, but these provisions were left out of the new draft as a result of staunch political opposition from Democrats.
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Their argument was that extending exclusivity would keep the price of new medications higher for longer, since it would keep generic drugmakers from producing them at a lower cost.
There is also the matter of establishing biomarkers as endpoints. In theory, the biopharmaceutical industry very much likes the idea behind this provision, but as now written, it seems to set current FDA practice in determining these biomarkers in stone-making it extraordinarily difficult, if not impossible, to establish new ones.
Failing to offer benefits to biotechs comes with a price. When the E&C Committee recently requested that the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO) share in paying for the proposed 21st Century Cures Act, the organizations gave E&C the cold shoulder.
And it's hard to blame them. They're already contributing about $80 billion to help defray the cost of the Affordable Care Act, as well as numerous other fees to cover FDA programs.
Biotechs, which are mostly small-cap R&D companies, don't enjoy the huge profits of the major pharmaceutical firms. In fact, many of them are still working toward their first profitable quarter. They can hardly afford to foot the bill for legislation that offers them nothing in return.
Without their financial contribution, the 21st Century Cures Act probably has no future-and perhaps that's for the best.
As written, it's hard to see how it will improve the time or cost of bringing new drugs to market, and in the end, may just add more layers of bureaucracy to an already incredibly complex system, as well as further entrench the FDA in antiquated practices.
The bill is still under discussion. It's not too late for the E&C to add provisions that work to the benefit of the bioscience industry. They could, for example, offer avenues for arbitration when a bioscience firm disagrees with an FDA rejection and has a reasonable argument to present. Or they could offer ways to sharply reduce the time required to resubmit a new drug application (NDA) after an initial rejection.
Anything that could actually reduce time and cost for most drugs going through the regulatory gauntlet would be welcomed.
But for the time being, those efficiencies remain unnamed and unrealized.
About the Author
Ernie Tremblay has more than 25 years of experience in following and analyzing the latest developments in health, medicine, and related technologies. He understands the FDA approval process, as well as the "hard science" behind new, experimental drugs and the market demand for them - and has a comprehensive grasp of the complex dynamics that determine whether a new drug will be a breakthrough winner, or just another casualty of the FDA approval process.