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Drug Development, Compassionate Use, and Adverse Events: A Cautionary Tale

by Alison, Bateman-House, Ph.D., MPH

In late September 2014, a man was admitted to the hospital due to vomiting, diarrhea, and fever. Suffering from a viral infection with no known cure, he was given an experimental antiviral medicine; unfortunately, he died. Maybe the experimental medicine did not work. Alternatively, maybe the man was too ill by the time the drug was administered for anything, no matter how effective, to work.

This patient’s name was Thomas Eric Duncan, and he captured media headlines as the first person to die of Ebola in the United States. The fact that his doctors tried an experimental drug called Brincidofovir on him also captured headlines, with his unfortunate fate directly impacting Chimerix, the small biotech company developing the antiviral drug. At the time that Duncan became ill, Brincidofovir was being studied in clinical trials for other types of viral infections, and it showed good efficacy and tolerability. This, plus the fact that no treatment for Ebola existed, made it reasonable for Duncan’s doctors to request that they be allowed to try treating him with Brincidofovir.

This single case can offer no insight into whether Brincidofovir is effective against the Ebola virus. If Duncan had survived, his survival may or may not have been due to Brincidofovir’s antiviral properties. Likewise, his death may, or may not, indicate that Brincidofovir is not effective against Ebola. What this case can do, however, is demonstrate how a public failure of an experimental drug can impact the company developing the drug.

Chimerix’s stock price had jumped after it was announced that Duncan’s doctors were going to try Brincidofovir. After his death was announced, Chimerix witnessed a nearly twelve percent fall in its stock price. For a small biotech company – particularly one with only one drug in its pipeline, as was the case for Chimerix – such a development could be fatal, ending the company itself and/or the development of the new drug. Chimerix got lucky: it was able to withstand the financial shock, and it and Brincidofovir remain in existence. Indeed, Brincidofovir is one of the handful of compounds that continue to be tested as a possible treatment for Ebola.

As seen in this case, drug companies can both be harmed and helped by reports of how their experimental drugs fare in non-clinical trial “compassionate use” contexts. However, repercussions on the company are more likely to be negative than positive, given that only a small fraction of drugs under development succeed as medical treatment. Furthermore, if a drug were to fail, it would be more likely to do so in an extremely ill patient, such as those for whom seeking an experimental treatment is their best available option.

If, after Duncan’s death, Chimerix had fallen, Brincidofovir development would have halted; perhaps permanently or perhaps just until another company had found a way to purchase development rights to the antiviral. Either way, a broad spectrum antiviral drug that was showing positive results in a Phase 3 clinical trial for the prevention of reactivation of Cytomegalovirus infections in adult hematopoietic stem cell transplant recipients and efficacy in treating adenovirus infections, would have been impacted. In the best case scenario, another company would have picked up Brinciofovir, completed the trials, and continue moving toward the U.S. Food and Drug Agency’s approval decision that will ultimate decide if the drug becomes available for sale and use in the United States. In the worst case scenario, the drug would have languished, the time, money, and effort spent to get it to Phase 3 of drug development testing wasted. Either way, there would be a real-world impact on patients who have need of antivirals.

Thus, compassionate use needs to be understood as not only a “last-ditch” attempt to treat one patient but also as an extra-clinical trial use of an investigational product that has real and potentially quite impactful consequences on the further development of that drug or device and thus on the patients who hope it will become a successful therapy.

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