Eleven years after approval, Entyvio remains the only IBD drug that acts only in the gut — and two large pharma programs have failed trying to replicate it.
Tysabri (natalizumab) blocks α4 integrin broadly — and 541 patients developed fatal brain infections. Entyvio (vedolizumab) blocks only α4β7, which binds MAdCAM-1 on gut endothelium. One Greek letter difference. Over a million patient-years, no REMS, no MRI surveillance. Takeda's $6 billion franchise is built on that subtraction — and on a head-to-head trial where vedolizumab beat Humira directly in ulcerative colitis.
Two drugs finally broke through. They work only before most patients are ever diagnosed.
Alzheimer's drug development has a 99.6% failure rate - the highest of any disease. Between 2003 and 2021, zero new treatments were approved while $42.5 billion was spent on clinical trials. Then lecanemab and donanemab broke through. But 27% slowing of cognitive decline, brain swelling in up to 1 in 4 patients, and $26,000/year raises the question: is this enough?
How a quiet antibody program in the Netherlands became the highest-revenue drug in pharmaceutical history.
Keytruda was invented at Organon in the Netherlands, buried in two acquisitions, and became a $32B/year franchise across 20 cancer types. Nearly half of Merck's total revenue now depends on one molecule. Its US patent expires December 2028.
It took 40 years to drug KRAS. The real competition started the day it worked.
KRAS mutations drive roughly 30% of all cancers. For four decades, no one could drug it. In 2021, sotorasib cracked the target. Now three approaches - next-gen G12C, G12D inhibitors, and pan-KRAS degraders - are racing to turn a proven mechanism into a blockbuster.
$6 billion in revenue. Generics launch May 2026. The decline already started.
Januvia was a $6 billion franchise for a decade. Generics launch in May 2026, but revenue is already down 64% from peak - squeezed by GLP-1 competition from above and generic anticipation from below.
