A Rapid-Learning Initiative For Cholesterol-Lowering Drugs

In late July, the Food and Drug Administration (FDA) approved selective use of Praluent, the first of a new class of cholesterol-lowering drugs (PCSK9 inhibitors). A similar drug, Repatha, is expected to be approved this month.

The reported results so far for Praluent, e.g. 50-70 percent lowering of cholesterol levels, are very promising — particularly for patients who are unable to control their cholesterol with statins. The new drugs may be uniquely valuable for a million or more persons with genetic conditions that cause high cholesterol. However, there is considerable uncertainty and debate about how broadly Praluent should be used. The initial listed price is high ($14,600 per year), and potential national spending on this new class of drugs could be billions of dollars annually.

Lowering cholesterol is not a guarantee of reduced heart attacks and strokes; such evidence for Praluent may be two years or more away. European regulators have approved Repatha, and are expected to approve Praluent for high-risk patients, with fewer restrictions than in the U.S. Market entry approval, however, leaves many unanswered questions about long-term benefits and side-effects and who—among tens of millions of individuals with high cholesterol—should take the drug.

Praluent and Repatha could be top candidates for an international “rapid-learning” initiative that uses the new comparative effectiveness research capabilities that the U.S. and other nations have developed in recent years. A successful initiative could be a model for testing of new cancer drugs and other technologies.

How can we learn as much as possible, as soon as possible, about the best uses of Praluent and Repatha, compared to other cholesterol-lowering drugs? Some of the new rapid-learning programs that could be coordinated include:

1. The Food and Drug Administration’s mini-Sentinel system for drug safety studies and post-marketing study authorities;
2. The Patient-Centered Outcomes Research Institute’s funding and networks for comparative effectiveness research;
3. The National Institute of Health’s Precision Medicine and Big Data To Knowledge (BD2K) initiatives, the National Cancer Institute’s MATCH clinical trials design for targeted drugs, and the National Heart Lung and Blood Institute’s cardiovascular research network; and,
4. The Center for Medicare and Medicaid Services’ “coverage with evidence development” authority to assess and price new therapies along with its Innovation Center funds.

A first step might be to convene a meeting of key interested parties, including patients, physicians, health plans, pharmaceutical companies, researchers, and government agencies (both U.S. and international). Participants could be asked to address these questions:

1. What do you need to know about Praluent and Repatha, compared to other cholesterol-lowering drugs?
2. What is the fastest and best system that could be designed for answering these questions? and
3. Who should carry out your proposed initiatives, and by when?

The goal is an international “action plan” for rapid learning, with tasks, accountabilities, and due dates.