The Drug That Took 25 Years to Prove a Radical Idea Could Work

What the Pivotal Trial Actually Showed

The VERITAC-2 trial compared Veppanu head-to-head against fulvestrant, a standard injectable hormone therapy, in patients with ER-positive, HER2-negative advanced breast cancer. In the ESR1-mutant group (270 patients), Veppanu delivered a median PFS of 5.0 months compared to just 2.1 months for fulvestrant.

That translates to a 43% reduction in the risk of disease progression or death (hazard ratio: 0.57, p=0.0001). The objective response rate told a similar story: 18.6% of Veppanu patients saw their tumors shrink meaningfully, versus only 4% on fulvestrant.

Now, let's be honest. Five months of progression-free survival isn't going to make anyone pop champagne. But context matters here. These patients had already failed prior therapy, and the comparison arm (fulvestrant) held them for barely two months. Overall survival data is still maturing, so the full picture isn't in yet.

One important caveat: in the broader, all-comers population (not just ESR1-mutant patients), the trial did not hit statistical significance. PFS was 3.7 months versus 3.6 months, with a p-value of 0.07. The drug's magic, at least for now, is confined to ESR1-mutant disease. That's why the FDA approved it with a companion diagnostic (Guardant360 CDx) to test for the mutation.

Wall Street Says: Buy the Platform, Not the Pill

Analysts aren't exactly modeling Veppanu as a blockbuster. The ESR1-mutant population is a slice of a slice of breast cancer, and the commercial rights have been licensed to Rigel Pharmaceuticals, with Arvinas and Pfizer collecting milestones and royalties rather than selling the drug themselves.

With Arvinas burning roughly $285 million per year on R&D, Veppanu's royalty stream alone won't turn the company profitable. The consensus? Veppanu is a proof of concept, not a profit engine.

The real value is validation. Before May 1, the biggest question hanging over every PROTAC program on the planet was simple: can this stuff actually get approved? Now that question has an answer.

The Floodgates Are Open

And there are a lot of programs waiting behind that gate. Arvinas itself has bavdegalutamide (ARV-110) in Phase I/II for prostate cancer, targeting the androgen receptor. Nurix Therapeutics is pushing BTK degraders for blood cancers. Kymera Therapeutics has IRAK4 and STAT6 degraders aimed at inflammatory diseases like atopic dermatitis. C4 Therapeutics is chasing BRAF and EGFR mutations in solid tumors. BMS inherited a molecular glue empire from Celgene and is building its own PROTAC portfolio alongside it.

The competitive landscape reads like a land grab. BeiGene, Astellas, Novartis, Roche, AstraZeneca, and Bayer are all building protein degradation programs. The theoretical appeal is irresistible: PROTACs could potentially target proteins that traditional drugs simply can't reach (transcription factors, scaffolding proteins, and other "undruggable" targets that make up a huge chunk of disease biology).

Why This Moment Matters Beyond Cancer

The 25-year journey from Crews's first chimeric molecule to a pill with an FDA label is, in many ways, the biotech equivalent of the Wright Brothers' 12-second flight. Nobody's crossing the Atlantic yet. Five months of PFS in a narrow patient population is a modest clinical result by any standard.

But what it proves is transformational. The human body's own protein disposal system can be hijacked, reliably and safely enough, to treat disease. The side effects were mostly mild (Grade 1-2), with QT interval prolongation on heart monitoring and liver enzyme changes flagged as key warnings on the label.

The modality works. The regulators are on board. And dozens of companies are now racing to prove it works against harder targets, in bigger populations, with even better results.

Twenty-five years ago, the idea of tricking a cell into destroying its own broken parts sounded like science fiction. Today, it's a prescription you can fill at a pharmacy. The first chapter of protein degradation is officially written. The interesting ones are just beginning.

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