Astellas, Pfizer look to broaden Xtandi's patient base with new prostate cancer win after 8 years

Astellas and Pfizer's Xtandi has been selling for over a decade, and the blockbuster androgen receptor inhibitor is still learning a new trick.

Xtandi showed it could work in non-metastatic hormone-sensitive prostate cancer (nmHSPC), the two companies said Friday. Both Xtandi alone and a combination of Xtandi and hormone therapy leuprolide beat leuprolide monotherapy in patients who had high-risk recurrence.

In a phase 3 trial coded Embark, both regimens staved off cancer metastasis or death, leading to “statistically significant and clinically meaningful” improvement over leuprolide alone, Astellas and Pfizer said. The trial has therefore met its primary endpoint and a key secondary goal.

Two other secondary endpoints also hit statistical significance, showing longer time to PSA progression and first use of new therapy for the experimental arms. Data on whether Xtandi could extend patients’ lives remain immature, but Astellas and Pfizer said investigators observed a positive trend. The study will continue to collect final overall survival information.

Astellas and Pfizer plan to discuss the data with regulatory authorities, including the FDA, to potentially file Xtandi for an approval in nmHSPC.

Friday’s news comes as Pfizer is shelling out $43 billion to acquire antibody-drug conjugate specialist Seagen to beef up its oncology portfolio. Pfizer got Xtandi through its $14 billion takeover of Medivation in 2014.

First approved by the FDA in metastatic castration-resistant prostate cancer (mCRPC) in 2012, Xtandi has become a standard of care in many stages of the tumor type. It added non-metastatic castration-resistant prostate cancer in 2018 and metastatic castration-sensitive disease in 2019.

While Xtandi has been on the market for over a decade, it’s still enjoying growth. For the nine months ended in December, Astellas reported a 24.4% sales increase from Xtandi to JPY 512 billion ($3.87 billion), although the growth came mainly from outside the U.S. For its share, Pfizer recorded $1.2 billion for Xtandi alliance revenue in 2022, roughly flat over 2021.

Compared with those treatment settings, nmHSPC represents an earlier stage of disease, in which there’s no detectable evidence of the cancer spreading, and the cancer still responds to testosterone-lowering treatments. About 20% to 40% of patients who receive definitive prostate cancer treatment experience recurrence within 10 years.

The Embark trial started more than eight years ago in late 2014. It focuses on nmHSPC patients with high-risk recurrence. These patients were initially treated by radical surgery or radiotherapy and still developed a fast surge in PSA, a protein biomarker.

Pfizer is also trying to pair Xtandi with other agents. The FDA recently granted priority review to Pfizer’s application to add its PARP inhibitor Talzenna to Xtandi in mCRPC. A phase 3 trial dubbed Talpro-3 is testing the Talzenna-Xtandi regimen in HRR-mutated metastatic hormone-sensitive prostate cancer and is expected to read out in late 2024.

In prostate cancer, Xtandi faces competition from three other androgen receptor inhibitors. Among them, Johnson & Johnson’s Zytiga is viewed as an inferior therapy with declining sales, while the New Jersey pharma’s Erleada is tracking growth.

Bayer’s Nubeqa looks to be a fierce competitor that’s rapidly gaining market share. Bayer recently dialed up its peak sales estimate for Nubeqa to $3 billion.