The Best-Selling Drug in History Just Lost a Head-to-Head Trial
A Chinese-invented drug just beat Merck's Keytruda on overall survival — a first. What it means for pharma's biggest franchise, the PD-1/VEGF gold rush, and Summit Therapeutics' $14 billion valuation.
(SEOUL) — On Sunday morning at the World Conference on Lung Cancer, a Chinese-developed drug did something no medicine has ever done: it beat Merck's Keytruda on overall survival in a head-to-head randomized trial.
Not progression-free survival, the softer endpoint that measures how long scans stay clean. Overall survival — whether patients are alive. In the Phase 3 HARMONi-2 trial, patients with PD-L1-positive advanced non-small cell lung cancer who received ivonescimab lived a median of 30.8 months, versus 22.6 months on Keytruda. That is an eight-month gap against the most successful drug in pharmaceutical history, a 27% reduction in the risk of death (hazard ratio 0.73, p=0.009).
To understand why this matters for markets, you need to understand what Keytruda is to Merck. Pembrolizumab did $29.5 billion in sales in 2024 — the best-selling drug on Earth, approaching half of Merck's entire revenue. It is the standard first-line treatment for the largest cancer indication in oncology, non-small cell lung cancer. And its key US patent protection begins expiring in 2028. Merck's entire equity story for the past three years has been a single question: what fills the hole?
The drug that just beat it was invented not in Rahway or Basel but by Akeso, a biotech out of Zhongshan, China. Ivonescimab is a bispecific antibody — one molecule that blocks PD-1 (Keytruda's target) and VEGF (Avastin's target) simultaneously. In late 2022, a then-obscure company called Summit Therapeutics licensed the Western rights for $500 million upfront — a deal engineered by Bob Duggan, the billionaire who built Pharmacyclics and sold it to AbbVie for $21 billion. Wall Street mostly shrugged.
It stopped shrugging in September 2024, when HARMONi-2 first read out: ivonescimab roughly doubled progression-free survival versus Keytruda (11.1 vs. 5.8 months). But skeptics had a ready answer — PFS is not survival, and VEGF-added regimens have a long history of shrinking tumors without extending lives. Show us overall survival, they said, expecting the effect to fade.
Sunday's late-breaker was the answer. The survival benefit was strongest exactly where the commercial stakes are highest: in PD-L1-high patients — the population where Keytruda monotherapy is the undisputed global standard — the hazard ratio was 0.58, a 42% reduction in the risk of death. Squamous histology, historically the hardest to treat: 0.65. Safety was broadly comparable, with no new signals on extended follow-up.
Summit's stock has responded: up roughly 35% since the survival win was first announced on September 2, closing near $18.40 today for a market capitalization around $13–14 billion — for a company with no revenue. Jefferies upgraded it to Buy last week.
So the obvious questions: Is the most important franchise in pharma now in managed decline? Is Summit — a pre-revenue biotech priced like a mid-cap pharma — still cheap, or already priced for perfection? There are three catches in this data that most of the coverage is skipping, and they determine both answers.
A free membership gets you access to every free article at AlphaBriefing.com: Join AlphaBriefing
The rest of this briefing is for paid members: the three catches in the HARMONi-2 data (including the subgroup where the benefit statistically disappears), the full PD-1/VEGF deal map — what Pfizer, Bristol Myers, and Merck each paid for their tickets — the catalyst calendar for Summit through 2027, and the scenario framework for both SMMT and MRK.
AlphaBriefing Paid gets you every investment thesis, scenario framework, and catalyst brief we publish — the analysis private intel clients pay four figures for, at a fraction of that.