How A Doctor Cured His Own Terminal Disease | Dr. David Fajgenbaum

KEYPOINTS

• 01

  Many treatments may already be sitting on pharmacy shelves

  Dr. David Fajgenbaum, a physician at the University of Pennsylvania and co-founder of the nonprofit Every Cure, notes there are about 4,000 FDA-approved drugs for roughly 4,000 diseases, while about 14,000 diseases have no approved treatment. Since a typical small-molecule drug binds 20 to 30 different proteins, many drugs likely have uses beyond their label. The system, he says, is not set up to find new uses for old medicines.

• 02

  Generic drugs lose their champions

  About 80% of approved drugs are generic. Once a patent expires, many manufacturers sell the same drug for pennies, so no one funds trials, pushes new uses into guidelines or educates doctors. Companies near a patent cliff usually tweak dose or formulation for the same disease rather than pursue a new one. Fajgenbaum stresses this is not a conspiracy; the incentives simply are not there.

• 03

  Cheap drugs with striking new evidence

  Aspirin has been shown to reduce colon cancer recurrence, particularly in tumors with a mutation in the mTOR pathway, yet many eligible patients do not take it. A trial in India of about 1,600 women with localized breast cancer, published in the Journal of Clinical Oncology, found lidocaine injected around the tumor shortly before surgery was associated with 29% lower five-year mortality. Every Cure is still reviewing the mechanism and evidence before advocating for it.

• 04

  The same mechanism can harm and heal

  Thalidomide caused devastating birth defects by blocking blood vessel growth. That same anti-angiogenic effect later earned approval for leprosy and multiple myeloma, saving thousands of lives. Sildenafil (Viagra) went from heart disease to erectile dysfunction to a rare pediatric lung disease. Colchicine, an ancient gout remedy, won approval at an adjusted dose to reduce heart attack risk in people who had already had one, particularly those with diabetes.

• 05

  Knowledge exists somewhere but fails to spread

  In DADA2, a genetic condition causing dozens of strokes from birth, a doctor around 20 years ago tried a leftover TNF inhibitor in one child and the strokes stopped. The finding spread slowly for about a decade until Chip Chambers, a physician whose two children were born with DADA2, helped gather data and guidelines. Fajgenbaum calls it a travesty: someone knew, but the world did not.

• 06

  How to advocate for yourself with a serious illness

  First, connect with the disease organization for your condition, such as the ALS Association or the Michael J. Fox Foundation, which often hear what is being tried worldwide. Second, find the world's leading expert and travel to them if you can. Third, keep asking questions, including whether anything else is being used elsewhere. Doctors read the literature in piecemeal ways and cannot keep up with millions of papers.

• 07

  He found his own treatment through repurposing

  As a third-year medical student, Fajgenbaum developed idiopathic multicentric Castleman disease, a cytokine storm that shut down his liver, kidneys and bone marrow. He nearly died five times. Seven-drug chemotherapy repeatedly saved him but did not hold. Testing his own blood and lymph node tissue, he found the mTOR pathway in overdrive and proposed sirolimus (rapamycin), a transplant drug never used for Castleman. He has been in remission for nearly 12 years.

• 08

  Breadcrumbs in published research can save lives

  In 2016 a man with metastatic angiosarcoma had been told he was out of options. A PubMed search turned up a 2013 paper showing four of five tumors expressed PD-L1. Treated with a PD-1 inhibitor, he has been in remission for nine years; the approach now helps about 18% of patients with a cancer once fatal within a year.

• 09

  Every Cure uses AI to rank drug-disease matches

  His lab's work has found 14 drugs for diseases they were not designed for. Every Cure scans all drugs against all diseases. Its top-ranked option for Castleman, the TNF inhibitor adalimumab, helped a patient who had failed other treatments; the case was published in the New England Journal of Medicine. A physician and patient must still make each treatment decision.