Drug development consultant Abby Bronson says early access to a new drug can jeopardize its full approval and long-term availability
Abby Bronson is the Duchenne muscular dystrophy program manager at Children's National Medical Center in Washington, D.C., where she works with various stakeholders to further therapeutic development for this disease. Bronson has a master's degree in business administration from the University of Pennsylvania and has managed new product development and marketing at biotechnology and pharmaceutical companies.
Q: What is the difference between expanded access for a new drug and accelerated approval of a new drug?
A: Accelerated approval is a change in the usual process of drug approval, but it eventually allows for collection of the same amount of safety and efficacy [effectiveness] data as the usual process.
An accelerated approval means a drug can be approved based on a shortened time frame because a biological indicator — “biomarker” — shows positive effects that are likely to correlate with clinical outcome. [The U.S. Food and Drug administration, or FDA, often refers to these biomarkers as "surrogate" markers, because they are stand-ins for "real" markers, such as survival or functional benefit.] There’s still a requirement for a confirmatory trial, and that trial might show that the drug does not work, that the biomarker was not valid. However, the FDA looks very carefully at these biomarkers, after a drug has gone through a standard phase 2 trial. And by that time, the safety of the drug has been pretty well established.
Expanded access, also known as compassionate use, can be applied for at any time during a drug’s development. It does not provide the same assurance of safety and efficacy as the full or accelerated approval process. [Expanded access can be granted for specific individual patients or specific categories of patients.]
Q: As soon as an experimental drug begins to show promise, no matter how preliminary the results may be, patients and families of patients with devastating diseases often demand access to the drug. From the point of view of a drug developer, what kinds of issues does this type of demand or request pose?
A: A company’s eye has to be on the goal of approval for a new drug. To do that, the company has to follow a strict path, one that is constantly monitored and has many reporting requirements.
When requests for compassionate use or expanded access come in, it requires a lot of resources for the company, which has to figure out where these will come from. The company has to decide whether it's going to take resources away from mainstream development to meet this request.
It takes about 100 hours to write an application for an investigational new drug — an "IND" — which is what’s needed for the FDA to allow expanded access or compassionate use. You have to find those hours by taking someone away from moving the main program forward, or you have to spend money to hire someone else — and that’s just to file the IND.
Then there’s monitoring of the drug. The drug company needs to present clean data to the FDA. Any kind of adverse event that a patient experiences while taking an unapproved drug could put the whole program on hold. Since it’s often the more severely affected patients who are being considered for compassionate use or expanded access, there’s a good chance that at least some adverse events will occur, whether or not they’re due to the drug’s effects, and that could slow down or even stop the drug’s development.
Then there’s supplying the drug for expanded access or compassionate use. It may be hard for a company to fully invest in the manufacturing process, because it’s not sure if it will ever get full approval for the drug.
There are also forecasting issues. How do you meet the demand for expanded access or compassionate use if you have limited resources?
Q: What do you wish patients and families understood about accelerated approval and expanded access — both of which allow patients access to drugs that are not fully approved by the FDA — that you believe many do not understand at this time?
A: Everybody wants to get the drug at the earliest stage possible. But the FDA’s phased trial process is designed to ensure safety and efficacy. With expanded access, you are shortcutting that process; you have not moved down that path as far. There is significantly more risk, and sometimes those risks can result in an outcome other than the one you wanted.
Q: Can you illustrate that with an example?
A: I know of a patient who had a rare form of kidney cancer and received treatment with an experimental drug through an expanded access program. The side effects were devastating. He experience extreme fatigue, loss of appetite and weakness, and he ultimately died. He was too debilitated to be given approved treatments that might have helped him, and he couldn’t go into another trial that might have been more promising, because he had already been on this experimental drug.
Q: Can the process of access to unapproved drugs be improved?
A: I think it is what it is. It has changed over time, reflecting the increased knowledge that patients and families have because of the Internet and other communication channels. But there's a perhaps irreconcilable difference between the perspective of an individual patient or family and that of society in general.
The view of the parent of a child with a devastating disease is, "Who cares about slowing down the process, or how much it will cost the company? I want this now for my child because it might help him." [Bronson says people may not understand how obtaining a drug early may slow down the full approval process and potentially jeopardize long-term access to the drug.]
But in the view of the FDA, the most important goal is to try to ensure that ultimately a drug can become available to everyone who needs it — and this is done by moving it through the approval process and demonstrating that it is safe and effective.
Four Perspectives on Expanded Access
This article is part of a Web-exclusive series titled Four Perspectives on Expanded Access, which includes the following articles: