Pfizer Inc. announced that the European Commission (EC) has approved TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. With this approval, TALZENNA is now the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations. This approval by the European Commission of TALZENNA in combination with XTANDI for the mCRPC indication is valid in all 27 EU member states plus Iceland, Liechtenstein, and Norway.

The approval is based on data from the Phase 3 TALAPRO-2 trial, a multicenter, randomized, double-blind, placebo-controlled study, evaluating two mCRPC patient cohorts: Cohort 1 (all-comers [n=805]) and Cohort 2 (those with HRR gene mutations [HRRm; n=399]). The results from TALAPRO-2 Cohort 1, which were published in The Lancet, showed that treatment with TALZENNA plus XTANDI reduced the risk of disease progression or death by 37% versus placebo plus XTANDI (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI], 0.51?0.78; P< 0.0001), meeting the study?s primary endpoint of improving radiographic progression-free survival (rPFS). At the time of the analysis, the median rPFS for those treated with TALZENNA plus XTANDI had not yet been reached versus 21.9 months for those treated with placebo plus XTANDI.

Median rPFS is defined as the timepoint in which 50% of patients in each treatment arms have progressed. A trend in overall survival (OS), a key secondary endpoint, favoring TALZENNA plus XTANDI was also observed, though these data are immature. The safety of TALZENNA plus XTANDI in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine.

TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. Pfizer has also shared the TALAPRO-2 data with other regulatory agencies to support regulatory filings. About Metastatic Castration-Resistant Prostate Cancer: Metastatic castration-resistant prostate cancer (mCRPC) is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone.

There were ~1.4 million new cases of prostate cancer reported worldwide in 2020, of which ~470,000 new cases were in Europe.1 Approximately 10%?20% of prostate cancer patients develop mCRPC within 5-7 years of diagnosis.2 Between 1.2%?2.1% of all prostate cancer cases globally are mCRPC. About TALAPRO-2: The Phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,106 patients with mCRPC (with no systemic treatments initiated after documentation of mCRPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=805) and those with and without gene mutations (HRRm; n=399).

Patients on androgen deprivation therapy (ADT) or who had bilateral orchiectomy in the trial were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160 mg/day. The primary endpoint of the trial is radiographic progression-free survival (rPFS), defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurs first, in both Cohort 1 (all-comers) and Cohort 2 (those with HRRm). Secondary endpoints include overall survival (OS), objective response rate, duration of response, and PSA response.

About TALZENNA® (talazoparib): TALZENNA (talazoparib) is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death. TALZENNA is approved in over 70 countries, including the U.S and the EU, as a once-daily monotherapy for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.

In the U.S., TALZENNA is approved in combination with XTANDI® (enzalutamide) for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). In the EU, TALZENNA is now approved in combination with enzalutamide for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.