Astellas surpassed market expectations in its third-quarter fiscal year 2025 results, as first-in-class cancer drug Vyloy defied a trial setback to deliver quadrupled sales.
As the first CLDN18.2 agent to reach the market, Vyloy saw sales swell (PDF) 426% to 19.5 billion Japanese yen ($125 million) during the last three months of calendar year 2025, which marked Astellas’ Q3.
In a Wednesday note, Jefferies analysts said they were “impressed by the rapid rise in demand” for the stomach cancer treatment.
The strong performance from Vyloy helped Astellas beat analysts’ expectations for total third-quarter sales by 8%, according to Jefferies.
Vyloy’s commercial surge comes after Astellas reported a midstage trial failure for the antibody in pancreatic cancer in October. At that time, Astellas said the impact of the trial setback on its financial results for the year was expected to be minor.
Moving into the earnings report, Astellas booked a loss of 12.8 billion yen ($82 million) in Q3, tied to the discontinuation of the pancreatic cancer program.
Also in pancreatic cancer, Astellas terminated ASP4396, a phase 1 KRAS G12D program, to focus on setidegrasib (ASP3082), another KRAS G12D protein degrader. The difference between the two drugs lies in their E3 ligase design. The prioritization decision was made because ASP4396’s data have yet to top its counterpart’s, despite being later in development, Astellas’ R&D chief Tadaaki Taniguchi said on a Feb. 4 earnings call.
A combination of setidegrasib and chemo recently posted a 58.3% objective response rate among 12 patients in first-line pancreatic cancer. Based on the results, Astellas plans to launch a phase 3 study in the indication by March, and it’s also planning registrational studies in non-small cell lung cancer.
Astellas would like to accelerate the development of setidegrasib in pancreatic cancer, Taniguchi said, noting that its competitor, Revolution Medicines, has not started a first-line pivotal study.
Last year’s clinical setback apparently didn’t dampen enthusiasm around the use of Vyloy in the closing months of 2025. During an investor call Wednesday, Astellas CFO Atsushi Kitamura attributed the drug’s commercial progress to “high Claudin 18 testing rates and lower-than-expected discontinuation rates.”
“By focusing on the prevention of nausea and vomiting, particularly in the initial cycle, we believe we can reduce discontinuation and enhance treatment continuation rate,” he said, according to a call transcript provided by Astellas.
Astellas is now testing Vyloy in combination with Merck & Co.’s Keytruda and chemotherapy in the phase 3 Lucerna trial in first-line stomach cancer. Enrolled patients have CLDN18.2-high, PD-L1-positive tumors. The company expects an interim readout in its fiscal year 2027 or later.
Besides Vyloy, Pfizer-partnered Padcev contributed about a third of Astellas’ overall Q3 sales growth. Sales of the star antibody-drug conjugate jumped 45% during the quarter, reaching 60.1 billion yen ($383 million).
In November, the FDA handed down a groundbreaking approval for a combination of Padcev and Keytruda as the first perioperative treatment for patients with muscle-invasive bladder cancer (MIBC) who can’t receive cisplatin-based chemotherapy. The indication was approved just a month after the FDA accepted Astellas and Pfizer’s application.
On a winning streak, the Padcev-Keytruda perioperative regimen was also said to have extended the lives of MIBC patients who are cisplatin-eligible in the phase 3 Keynote-B15 (EV-304) trial.
Doctors have already started using Padcev in perioperative MIBC, Claus Zieler, Astellas’ chief commercial and medical affairs officer, said during the Feb. 4 investor call. But he cautioned that, based on Astellas’ experience with past Padcev indications, there will be “a very sharp plateau” after “a very fast uptake” in the first six months of rollout as the company tries to penetrate the new patient population completely.
Thanks to the strong performance of Padcev and Vyloy, Astellas raised its full-year fiscal 2025 revenue forecast by 10% to 2.1 trillion yen. The company collected 1.6 trillion in the nine months that ended in December.
Padcev and Vyloy are two of Astellas’ five strategic brands, which together are nearing 500 billion yen sales on a full-year basis, Kitamura said.
Astellas is pinning its future on the strategic brands—which also include menopause therapy Veozah, eye med Izervay and leukemia drug Xospata—as its Pfizer-partnered prostate cancer juggernaut Xtandi nears a 2027 U.S. patent cliff. In Q3, Veozah and Izervay expanded sales by 28% and 33%, respectively, while Xospata was relatively flat.
In the pipeline, Astellas has highlighted four “primary focus flagship programs.” Besides setidegrasib, the group also includes ASP2138, a CLDN18.2xCD3 bispecific; AT845, a gene therapy designed for Pompe disease; and ASP7317, a cell therapy for geographic atrophy.
In Q3, Astellas reports that it achieved proof of concept for ASP2138 in first-line stomach cancer and is now preparing to launch a phase 3 trial.
“This is very good news because it means that Astellas now has a healthy-looking late-stage R&D pipeline,” the Jefferies analysts said. “This, matched with its fast-growing portfolio of on-market products, is likely to broaden the appeal of Astellas' stock to a broader group of investors.”