Compassionate Drug Access: A Real Option for Cancer Patients?

A recent New York Times article tells the story of one woman’s quest to gain access to an experimental drug to treat her deadly cancer. Her story is familiar to many of us who have heard similar tales; a cancer patient runs out of treatment options, but with the help of proactive oncologists is able to receive a new, investigational drug; that is, a drug not yet approved by the U.S. Food and Drug Administration (FDA). This last-resort treatment approach is known as compassionate use or, as the FDA prefers to call it, expanded access. The U.S. National Library of Medicine explains:

“Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.”

The concept is simple, but a patient or oncologist seeking expanded access faces a complex process full of uncertainty. There are several criteria that must be met before making a request for expanded access:

-The patient must have a life-threatening cancer for which there is no FDA-approved therapy available.
-The patient must be unable to participate in a clinical trial.
-The potential benefit of using the treatment must outweigh the potential risk.
-The drug that is being sought must have completed safety studies in humans (i.e., a phase I clinical trial).
-Individual access to the drug should have no impact on the completion of ongoing clinical trials of the drug or the drug’s approval and should not impair enrollment in clinical trials.

Assuming that the above criteria are met, a ‘single patient IND’ application must be filed (IND stands for Investigational New Drug). More information can be found at the FDA’s website, and the process is outlined here:

A patient (or treating oncologist) should have detailed information about the investigational drug he or she believes could be suitable for the patient’s condition. The majority of investigational cancer drugs in industry pipelines are targeted therapies. Targeted therapy drugs target specific genetic mutations, so fairly comprehensive information on the genetic alterations in the patient’s tumor must be gathered via molecular testing. This is not yet a widely accessible type of analysis, but there is growing use of tests like Foundation One, which screens for many of the genetic mutations found in cancer.

Other options for investigational drugs may include immunotherapies. A patient might be interested in gaining access to an immunotherapy drug that is being tested in a limited number of cancers, but is not yet available in trials for his or her specific type of cancer. (It can be more difficult to gain expanded access to these drugs than to targeted therapies.)

Once these hurdles are jumped, an expert in the field of targeted (or immuno-) therapies should match genetic mutations in the patient’s tumor with an IND that is currently being tested on patients in one or more clinical trials.

Next, the treating oncologist, equipped with this information, should initiate the process of gaining access to the drug. The oncologist must seek approval from his or her hospital’s Institutional Review Board (IRB). However, some oncologists might not be willing to go through this relatively complicated process. Also, not all hospitals even have an IRB, in which case the oncologist could try to seek IRB approval in a medical center that does have one; this might involve a fee.

However, IRB approval does not mean that the manufacturer of the drug will actually provide the drug to the oncologist. Clinical trials and the information they provide on drug safety and efficacy are the only means by which a drug company can eventually move a drug toward marketing. Drug companies might therefore not see any benefit in expanded access because no information will be gained that could expedite drug approval by the FDA. In addition, the drug company might charge a fee for expanded access use, and this fee will not be covered by most insurance plans.

Finally, if the drug company agrees to provide the drug—and therefore become the ‘sponsor’—the FDA must approve the treatment protocol. If the sponsor has already submitted an IND protocol for clinical trials, it does not have to submit a new single patient IND application, but must add an ‘access protocol’ to the existing one. Alternatively, the treating oncologist can submit the access protocol, but only with the sponsor’s approval. Both options are time consuming.

Either way, the sponsor (drug company) ultimately has the last word in the process.  In May of this year, the FDA actually announced a set of rules called ‘Guidance for Industry‘ that defines the terms of expanded access in a lengthy document. But these rules are not binding and are not designed to force drug companies to provide drugs for compassionate use.

The hurdles of accessing investigational drugs were conveyed by the recent New York Times article. The story’s subject had been threatened by an incurable lung cancer. She hoped to gain access to investigational drugs: first crizotinib (now FDA-approved), followed by LDK378 (not yet FDA-approved). Her efforts were ultimately successful and her life was prolonged by several years as a result of these experimental treatments. This patient, however, had some key connections in medical circles. These connections made her appeals to drug companies work and allowed her to move past obstacles that might otherwise have proven insurmountable.

Clearly, the vast majority of cancer patients have no well-placed friends in medical centers or regulatory agencies or drug companies. However, every patient has access to one or many patient advocacy groups. One of the many roles of advocacy groups is to guide patients to investigational drugs by promoting enrollment in clinical trials. Facilitating expanded access for patients who need it should become another goal of advocacy groups. In order for advocacy groups to achieve this, they must also lobby drug companies to provide expanded access to individual patients whenever possible.

A framework for investigational drug use is badly needed, as has been discussed on many occasions, including in a 2008 paper in the Journal of the American Medical Association. Trying to limit the role of the FDA in the expanded access process, preventing drug companies from charging exorbitant prices for expanded access/compassionate use, and creating incentives for the investigators (oncologists) driving the process could help shape this framework so that more patients can access drugs they need.

It should be noted that some drug companies have programs known as expanded access trials. (These can be found on by searching for ‘expanded access’; there are at least 47 such trials for cancer.)  The aforementioned lung cancer drug LDK378 is provided through an expanded access trial. Novartis made LDK378 available under expanded access in trial number NCT01947608 in September, 2013. The trial, being run at 30 locations, is for lung cancer patients with a mutation in the ALK gene who have been treated with the approved drug crizotinib, but did not respond or experienced recurrence—just like the woman whose plight was described in the New York Times article. The trial is specifically for patients who have no access to LDK378 through regular clinical trials. Meanwhile, LDK378 has already shown so much promise in regular clinical trials that it has received breakthrough therapy designation from the FDA, and will most likely be approved for marketing soon. But not soon enough for some patients.