Daniel S. Levine

The FDA wants to make it easier to gain access to experimental medicines for patients with serious illness who are without therapeutic alternatives. That may be good news for people with a dire prognosis and no available therapies, but the FDA itself is not the problem.

In a recent blog, FDA Commissioner Scott Gottlieb announced that the agency was simplifying the process for physicians who apply to FDA to use an investigational drug to treat their patient.

Prior to treating a patient under expanded access, physicians must obtain approval from the Institutional Review Board at their facility. To simplify the process for physicians seeking access to an investigational product to treat their patient, Gottlieb said going forward, a single IRB member—the chair or another appropriate person—can now approve the treatment.

That’s all well and good, but rarely is it the FDA that stands as the obstacle to patients getting access to experimental therapies. In fact, the FDA gets about 1,000 applications a year for so called compassionate use. The agency authorizes about 99 percent of these requests. The real problem is the risk and reward calculation for drug companies, who make the ultimate decision whether to supply a drug or not.

“FDA recognizes that time is critical for these seriously ill patients who do not have alternative therapies, and who cannot take part in a clinical trial of an investigational therapy,” wrote Gottlieb.

There are a number of reasons why pharmaceutical companies may not want to provide an experimental therapy through compassionate use. There may be a limited supply of drug for clinical trials. They may also fear that providing drug through this means would discourage people from participating in clinical trials, or that they may be taking on unnecessary legal liabilities. But the real stumbling block is a simple risk/reward calculation.

Drugmakers may have hundreds of millions of dollars invested in the development of a drug. They may have a great deal of their value tied to the success of that drug. And, there’s the population of patients that a company may be developing the drug to treat that need that drug.

Compassionate use of an experimental therapy is a clinical trial of one. The use of the drug in that patient is tracked and reported, although the conditions of its use may be less rigorous. Patients who access drugs in this way are usually quite ill and their health may be well outside the range that a drug company would want for inclusion in a clinical trial. They may also be using the drug for an indication it is not being developed to treat.

Drugs sometimes are approved through narrow margins. While drugs must demonstrate efficacy, what’s often more likely to kill a drug is concern about its safety. Drugmakers fear that a patient using a drug through compassionate can skew the data and create enough concerns about its safety that it may kill a program, wiping out investment, destroying value, and preventing patients more broadly from getting access to the drug.

The FDA is aware of this. In fact, Gottlieb acknowledged this in his blog.

“We’ve seen some reluctance among companies to provide investigational drugs for expanded access. This may have been due, in part, to uncertainty about how data for adverse events that occur during treatment under expanded access are viewed by FDA. Companies have voiced concerns that any apparent negative effects might jeopardize the product’s development,” he said. “We recognize that patients receiving expanded access are usually treated outside of a controlled clinical trial setting. As a result, they may have more advanced disease than clinical trial participants, be receiving other drugs at the same time, and have other diseases. FDA recognizes that these factors make it more difficult to determine the cause an adverse reaction.”

If the FDA really wants to improve access to experimental therapies to patients who are desperate and may feel they have little to lose,

To clarify how the agency views adverse event data in these circumstances, it recently updated industry guidance on expanded access. The guidance clarifies that suspected adverse reactions must be reported “only if there is evidence to suggest a causal relationship between the drug and the adverse event.”

While the agency is taking other steps to promote expanded access, it’s unlikely that its clarification will do much to change the risk/reward balance for drugmakers. Patients facing death will see little risk in experimenting with an unproven therapy for their disease. FDA has little to lose by encouraging access to experimental therapies for these patients. But drugmakers have little to gain and much to lose. If the agency is committed to making compassionate use more available, it will need to find a way to do more to eliminate the risk to drugmakers.

October 4, 2017

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