The Benefits of Accelerating Drug Approvals for Rare and Orphan Drugs

A new proposal would allow drugmakers to bypass some of the most expensive and time-consuming studies in the clinical trial process.

Rare disorders are generally considered to affect fewer than 200,000 patients, but according to the National Institutes of Health, there are 7,000 rare diseases affecting 25 million Americans (http://report.nih.gov/NIHfactsheets/Pdfs/RareDiseasesClinicalResearchNetwork(ORDR).pdf). In some cases, the number of patients with a particular disorder is fewer than 5,000 across the nation. Developing agents to treat these patients can be a great gamble for pharmaceutical companies, and if they do reach the market with an effective product, they tend to be priced high to help defray the development costs and gain a profit (because of low anticipated utilization of the agent).

Related to this, payers worry that the costs of many newer drugs developed to treat rare conditions are extremely high—over $100,000 per year—and even a few patients on their membership rolls can mean substantial budget impact.

A new proposal introduced by a Democratic senator from North Carolina would allow drugmakers to avoid some of the most expensive and time-consuming studies in the clinical trial process in an effort to bring these agents to market sooner. Working in concert with the Biotechnology Industry Organization, Senator Kay Hagen wants to broaden the use of the Food and Drug Administration’s (FDA) current Accelerated Approval process to more quickly bring new pharmaceuticals to patients who may benefit from these agents.

Under this proposal, the industry can bypass phase III clinical trials as a requirement for approval. Instead, the manufacturer would be able to use phase II trial data showing the measured effect of a drug. After receiving marketing approval, the manufacturer would then be required to show that outcomes are actually improved.

Bloomberg News Service (http://www.bloomberg.com/news/2011-11-16/drugs-for-unmet-needs-may-get-faster-approval-under-senate-plan.html) illustrated how this would work: For a particular cancer, if a drug demonstrated in phase II trials shows the ability to shrink tumors, then that may be sufficient for drug approval. After the FDA approves the agent for marketing, the manufacturer would then have to show that the anticipated survival benefit is attained.

One promising benefit of this accelerated program is that with the elimination of pre-approval for phase III trials, it is possible that the cost of introducing new agents for the treatment of rare diseases would be significantly reduced. If this is the case, perhaps the price of the agents to payers and patients would be reduced (as the amount needed to recoup the investment is lower).

This proposal to shorten the approval process has two obvious concerns: patient safety and questions about drug effectiveness. The industry argues that the current Accelerated Approval process does not result in worse outcomes. But this is a murky argument in cases that are life-threatening, such as cancer. Since 2006, the FDA has approved 85 treatments for rare diseases, using limited clinical trial data. Furthermore, the European Union has implemented such a program with positive results. It seems that for rare diseases where there is unmet need, conditional approvals that require ongoing trials will allow patients access to the product at an earlier time.

The FDA’s current accelerated review process is limited to pharmaceutics to treat life-threatening diseases for which there are unmet needs. Under today’s accelerated review, the FDA grants conditional approval to products to treat conditions like cancer or acquired immunodeficiency syndrome. When a product undergoes post-launch studies that demonstrate improved outcomes, the FDA then grants full approval.

This proposal has been introduced as part of talks to renew the biopharmaceutical companies’ funding of the FDA’s operations through the Prescription Drug User Fee Act (PDUFA). Under current proposals, the industry would pay more than $712 million in 2013 to fund FDA activities.

This proposal has considerable promise, particularly for the millions of Americans who may get quicker access to treatments for rare disorders. However, it will be up to the industry to ratchet down the price of therapies once they are approved.