How RAS went from "undruggable" to Rasonque, the first RAS-targeted medicine to extend survival in pancreatic cancer, and the best reporting and science behind it.
For 40 years RAS was "undruggable." On August 26, 2026 the FDA approved daraxonrasib (Rasonque), the first broad RAS-targeted medicine for metastatic pancreatic cancer, after the RASolute 302 trial nearly doubled overall survival (13.2 vs 6.7 months, HR 0.40). The discovery, the data, the approval, and what comes next, told through the best reporting and science, each tagged free, open-access, or subscription.
Several companies want to stretch IBD antibodies from a shot every few weeks to one every three months, or even six. Keeping the drug in the blood that long is the easy part. Whether the disease stays controlled right up to the next dose is the hard part, and the bet the newest programs are making.
“Long-acting” hides three claims: the drug stays in the blood (PK), keeps blocking its target (PD), and keeps the disease controlled (durability). Only the last proves a long interval works. Across 1,147 IBD trials, TL1A is the most crowded emerging target, with 7 antibodies, 6 sponsors and 36 trials, and 3 already in Phase 3. The leading long-acting candidates report 56–85 day half-lives, a 3–5× leap. But the trough, how much drug is left at the next dose, tells the real story: at the proposed quarterly and six-month intervals it sits at roughly 19–47% of peak, inside the range today’s biologics already tolerate. The PK was never the wall; durability is, and only XmAb942 is yet testing a long interval in patients.
Two of the newest PsA drugs block IL-17F as well as IL-17A; the older ones block only IL-17A. A plain walk through what the extra target actually buys: clear help on the skin, no proven help on the joints yet, and a fungal cost in the middle.
Sonelokimab met its Phase 3 endpoint in psoriatic arthritis in August 2026, the second drug engineered to neutralise IL-17F alongside IL-17A. The first, bimekizumab, is already approved; secukinumab and ixekizumab block IL-17A alone. On the joints, the dual drugs post ACR50s around 43–44% versus 35–40% for the A-only incumbents — but the trials aren't comparable, so the gap isn't proof. On the skin the story firms up: PASI90 around 61–69% versus 33–49%, plus a head-to-head in psoriasis where bimekizumab out-cleared secukinumab. Blocking IL-17F looks like a skin benefit, not yet a joint one.
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.
