- A combination of Seagen’s antibody drug Padcev with Merck & Co.’s immunotherapy Keytruda could become standard treatment for bladder cancer after clinical trial results presented Sunday showed a large survival benefit over chemotherapy.
- The two-drug regimen cut the risk of death by more than half compared to chemo, improving by 15 months the median overall survival among trial participants given the experimental combination. The data, which were unveiled at the European Society of Medical Oncology’s annual meeting in Spain, exceeded expectations held by analysts.
- Padcev and Keytruda also reduced the risk of disease worsening or death — a broader measure of benefit known as progression-free survival — by 55% over chemo. No new safety issues were identified in the study, Seagen and development partner Astellas said in a statement.
Seagen and Astellas’ trial data are significant for the future use of Padcev in bladder cancer and could serve to confirm the drug’s accelerated U.S. approval for first-line, or previously untreated, bladder cancer.
Stephen Wiley, an analyst at Stifel, wrote in a Monday note to clients that the data will "cement" the pairing of Padcev and Keytruda as the standard-of-care in the first-line setting, and "likely transform Padcev into a multi-billion dollar franchise."
The data are also important for Merck, which is relying on new treatment combinations to further entrench use of Keytruda across cancer types, and for Pfizer, which is in the process of acquiring Seagen for $43 billion. Shares in the latter pharmaceutical company rose by as much as 2% Monday morning, while Merck’s stock ticked up 1% in value.
“The [bladder cancer] result bridges the Merck of the last decade to the Merck of the next decade,” Leerink analyst Daina Graybosch wrote in a note to clients, describing how the pharma aims to prove antibody-drug conjugates, or ADCs, like Padcev can replace older platinum-based chemo drugs.
“Rather than one drug for all situations in [Keytruda], they are building an arsenal of ADCs that they envision developing with precision across indications and combinations on top of [standard of care] and beyond,” she added. (On Friday, Merck announced a major alliance with Daiichi Sankyo that gives it rights to three experimental ADCs.)
The bladder cancer trial, which Seagen and Astellas ran with Merck, enrolled 886 people who had previously untreated locally advanced or metastatic urothelial cancer and were eligible for platinum chemo. Participants were randomized to receive either Padcev and Keytruda together or chemo.
Trial volunteers on the combination arm lived a median of 31.5 months versus 16.1 months among those given chemo. Median progression-free survival was 12.5 months for Padcev and Keytruda compared to 6.3 months for chemotherapy.
The benefit was consistent across different subgroups, such as whether patients’ tumors expressed a biomarker called PD-L1, Seagen and Astellas said.
The most common side effects included rash, high blood sugar, low white blood cell counts and nerve pain.
Padcev was approved in the U.S. in 2019 for later-stage treatment of bladder cancer. It was Seagen’s second drug to reach market and helped boost the company’s value at a time when more large drugmakers were becoming interested in the potential of ADCs.
In April, the Food and Drug Administration granted Padcev a conditional OK for use in previously untreated bladder cancer patients who aren’t eligible for cisplatin-containing chemo. The therapy is being studied together with Keytruda in several other clinical trials, including two Phase 3 tests.