Pfizer’s Talzenna has been holding onto a breast cancer nod while three other marketed peers battle it out in ovarian cancer. But with a pivotal trial win, the PARP inhibitor outlier is poised to join the fight in a more competitive tumor type.
Adding Talzenna to Pfizer and Astellas’ androgen receptor inhibitor Xtandi significantly staved off tumor progression or death in patients with metastatic castration-resistant prostate cancer (mCRPC), Pfizer said Tuesday. The benefit was achieved in men with or without homologous recombination repair (HRR) gene mutations.
While detailed results from the phase 3 TALAPRO-2 study won’t be available until an upcoming medical meeting, Pfizer is already talking up blockbuster sales potential for Talzenna, a drug that has remained silent for the past four years.
“Based on these compelling combination data with Xtandi, we believe Talzenna in prostate cancer may become the next potential blockbuster opportunity in our leading Pfizer oncology portfolio, subject to regulatory approval,” Suneet Varma, Pfizer’s global oncology and U.S. president, said in a statement Tuesday. Pfizer acquired both Xtandi and Talzenna in 2016 through its $14 billion acquisition of Medivation.
TALAPRO-2 tested the Talzenna-Xtandi combo in patients who hadn’t received prior systemic cancer treatment for prostate cancer. The positive readout follows a similar win by AstraZeneca and Merck & Co.’s Lynparza in a broad newly diagnosed population regardless of HRR mutation status and a smaller win by Johnson & Johnson for Zejula in HRR-mutated patients. Both Lynparza and Zejula were paired with J&J’s androgen receptor inhibitor Zytiga in their respective trials. J&J obtained Zejula prostate cancer rights in a 2016 deal with Tesaro, which later became part of GSK. J&J has not unveiled a new brand name for Zejula in the investigational indication.
While Zejula may be out of the picture for a broad label with non-HRR-mutated patients, Talzenna looks it could put up a fight against Lynparza, currently the market-leading PARP agent.
In the phase 3 PROpel trial, the Lynparza-Zytiga combo pared down the risk of progression or death by 34% over Zytiga alone. In its Tuesday release, Pfizer said Talzenna’s addition to Xtandi led to a progression or death risk reduction that was greater than 30.4%, which was the TALAPRO-2 trial’s prespecified target.
What’s more, the Talzenna-Xtandi combo gave patients a progression-free survival time that “appears to be the longest observed in a randomized trial in this setting,” Chris Boshoff, M.D., Ph.D., Pfizer’s chief development officer for oncology and rare disease, said in Pfizer’s Tuesday statement.
Data on whether the Talzenna pairing can further extend patients’ lives remain immature, but the results showed a trend toward improvement at this time, Pfizer said.
And while the trial has met its goal for all patients regardless of HRR status, it wasn’t yet able to report the same for a cohort of patients with HRR mutations. PARP inhibitors like Talzenna typically work best in tumors with BRCA mutations, which belong to the HRR mutation category.
Talzenna is currently only approved for germline BRCA-mutated, HER2-negative advanced breast cancer, thanks to an FDA nod in 2018. And that approval came months after Lynparza’s first-in-class nod in the same indication. The small indication has not enabled Talzenna to generate enough sales to appear on Pfizer's annual report.
By comparison, Xtandi, as a standard of care in mCRPC, reeled in 534.3 billion Japanese yen ($3.7 billion) of sales for Astellas in the twelve months ended in March, up 16.6% year over year. Pfizer recorded $1.2 billion from Xtandi alliance revenue in 2021.
Further pressuring Talzenna’s presence, Lynparza in March moved earlier in the treatment line to become the first FDA-approved adjuvant treatment for use after surgery against BRCA-mutated high-risk early breast cancer.
Besides mCRPC, Pfizer is also combining Talzenna and Xtandi in HRR-deficient metastatic castration-sensitive prostate cancer in the TALAPRO-3 trial.