Our interview this week is all about repurposing medications. Hundreds of rare diseases don’t have effective treatments. Even some common conditions lack approved therapies. The research to develop new medications to manage or cure them is costly and time-consuming. Is there a way to teach old drugs new tricks? That could allow us to repurpose existing pharmaceuticals for hard-to-treat conditions.
Our guest, Dr. David Fajgenbaum, was a healthy young medical student who inexplicably became deathly ill. Multiple organ systems were failing, and his doctors did not know why. (You can listen to the full story here.)
Eventually, they did reach a diagnosis: idiopathic multicentric Castleman disease. Essentially, his immune system had turned against him and was attacking his organs. But diagnosis was not enough. Castleman disease is rare, and the treatment his doctors prescribed was not effective for Dr. Fajgenbaum. He nearly died four times.
That convinced him to try to find a medication that would work to keep his condition under control, even if the FDA has not approved its use against Castleman disease. He was successful in repurposing a drug used to prevent organ transplant rejection, sirolimus. It has now helped him stay alive and productive for years.
When the world-wide pandemic of COVID-19 appeared, there were no drugs approved to treat it. The infection had never been studied before. As a result, scientists scrambled to come up with ways to control the coronavirus. Two existing medications, dexamethasone and tocilizumab, turned out to be life savers.
The steroid dexamethasone reduced the death rate of hospitalized patients on oxygen (NEJM, Feb. 25, 2021). It was readily available and inexpensive.
The immune-suppressing medicine tocilizumab, while pricier and less dramatic than dexamethasone, also lowered mortality. That was among hospitalized patients needing ventilation who were also getting steroid treatment (JAMA Network Open, Feb. 28, 2022).
Dr. Fajgenbaum and his colleagues are studying nine drugs that may end up being very helpful against disorders that need better treatments. Not all of them are as old as sirolimus or dexamethasone. One example is pembrolizumab, also known by its brand name Keytruda.
The FDA has approved this monoclonal antibody for treating several malignancies, including melanoma, non-small cell lung cancer, Hodgkin lymphoma and several others. Because it works, in part, by suppressing PD-L1, they suspected that it might help a person who sought their help for a life-threatening angiosarcoma. Fortunately, it worked for this patient. But to find out if it will work for others, they will need to conduct a clinical trial. Keytruda is not a benign drug. A clinical trial is the only to find out if the benefits outweigh the risks.
During our interview with Dr. Fajgenbaum, we discussed BCG (Bacille Calmette-Guérin), a hundred-year-old vaccine against tuberculosis. Could it be helpful for COVID-19 or other infections? As we noted, it is already approved for treating bladder cancer. Might it be helpful against other tumors?
Investigators will need to overcome several barriers to make the dream of repurposing old drugs a reality. Currently, there is no central data repository on drug trials. The manufacturers may keep their own databases, but they don’t share with other scientists. As a result, it was partly luck that led Dr. Fajgenbaum and his colleagues to consider Keytruda for the angiosarcoma patient.
Another barrier is the lack of a business model that will reward the research. Once a drug goes off patent, usually generic manufacturers bring out their versions at a lower price. While this is helpful for patients, it means the manufacturer has no interest in pursuing research that could teach their old drugs new tricks.
In addition, no organization is responsible for overseeing this “post-hoc” drug development. The FDA is primarily focused on new drug approvals. In the US, we do not have an agency or administration devoted to making sure that all of our medications reach their full potential. Dr. Fajgenbaum is hoping that his nonprofit organization EveryCure can pick up the slack in this area.
David Fajgenbaum, MD, MBA, MSc, is Assistant Professor of Medicine at the Perelman School of Medicine of the University of Pennsylvania. He is Founding Director of the Center for Cytokine Storm Treatment & Laboratory (CSTL) and Associate Director for Patient Impact of the Orphan Disease Center at the University of Pennsylvania. In addition, Dr. Fajgenbaum is Co-Founder & President of the Castleman Disease Collaborative Network (CDCN).
Dr. Fajgenbaum is a physician-scientist of immunology and co-founder of the non-profit EveryCure, www.everycure.org. His book Chasing My Cure: A Doctor’s Race to Turn Hope Into Action.
© 2023 The People's Pharmacy
All Rights Reserved