Monday, March 30, 2015

Wanted: Guidelines for Access to Experimental Drugs

Critically ill patients need new medicines, but what if this slows FDA approval for future patients?

By Kenneth I. Moch. This post was originally published on the Wall Street Journal      
A year ago this month a social-media crisis thrust a set of complex ethical questions and dilemmas onto life-science companies. The family of a 7-year-old boy turned to patient advocates and social media to pressure Chimerix, a small biotech company of which I was CEO, to provide access to an experimental drug, brincidofovir, to fight his life-threatening viral infection.

Over five days Chimerix became the focus of a social-media wave that rapidly spread into the global mainstream media. Josh Hardy would get the drug, but the patient advocate who led the campaign has said he would have “destroyed Chimerix” if Josh hadn’t.

Expanded access, more commonly called “compassionate use,” provides an experimental medicine to treat a seriously ill individual who has no other options. Because these requests generally occur prior to completing clinical studies designed to determine safety and efficacy, there may be only limited understanding of the drug’s risks and benefits given the patient’s specific medical situation. Moreover, a patient may want the medicine for a different disease or condition than the one for which it is being developed.

Requests for expanded access increased 92% in 2014, a trend that will continue. In the aftermath of Josh Hardy’s story and others, eight state legislatures have enacted and over 20 are considering “right to try” laws, under which terminally ill individuals are deemed to have a “fundamental right” to receive experimental medicines and devices via expanded access. Last month the Food and Drug Administration took steps to simplify the expanded access application form for physicians.

Life-science companies now bear nearly the entire weight of deciding requests for expanded access. Management teams must balance the near-term needs of the individual versus the longer-term needs of the population, with little to guide them.

Should pressure from social media or special connections play a role in whether a patient receives an experimental medicine? Should a company avoid any risks to a development program in order to help a larger number of patients in future years? If there are a limited number of doses available, how should a company choose which patients receive the medication?

What if a critically ill patient gets worse or dies for reasons unrelated to the experimental drug, but because of an ensuing uproar other patients decline to participate in clinical trials? Who is advocating for future patients who, because of slower clinical-trial enrollment or unexpected events, might not receive a needed medicine because FDA approval is derailed or delayed by even a month?

These ethical decisions should not rest solely on corporate leadership. Instead, there needs to be a focused effort to create a more equitable approach to expanded access. Here are several proposals:

• Life-science companies should publicly state their policy on expanded access. It must be recognized that a company has the right not to make an experimental medicine available if it believes the greater good is served by this decision.

• Regulatory guidance should provide a framework so companies can consider the risks to the drug development timeline and approval pathway in the face of unforeseen or unfortunate consequences from granting expanded access.

• Especially for smaller companies whose drug or device may be their only product, there should be an optional system to provide support for these complex decisions. Last August New York University bioethicist Arthur Caplan and I proposed an independent “Expanded Access Institutional Review Board,” which could help companies weigh multiple factors, including equitable access and availability, cost, and the short- or long-term risks and benefits to a development program.

Josh Hardy received brincidofovir, but not under expanded access. With extraordinary collaboration from the FDA, Chimerix initiated a new Phase 3 clinical trial that has recently shown the drug’s potential to reduce the mortality rate of the virus that was killing Josh. He was the first patient enrolled in the trial, rapidly responded to the drug, and now is approaching his 9th birthday.

This positive outcome should not lead anyone to assume that there is a simple, monolithic solution to expanded access. Each drug is different, the testing and data required for FDA approval are different, and patient populations are different. Expanded access is not a substitute for clinical trials.

Our current system is rife with ethical dilemmas and is not equitable. If we want critically ill patients to receive experimental medicines as a last resort, we need to find a balance between the immediate needs of individual patients and the equally important needs of future patients.

About the Author: Mr. Moch has been co-founder or CEO of four companies developing therapies for life-threatening diseases and most recently was the president and CEO of Chimerix In.

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