FDA Approves New Abiraterone Acetate Formulation for mCRPC

The FDA has approved a new formulation of abiraterone acetate (Yonsa) in combination with methylprednisolone as a treatment for men with metastatic castration-resistant prostate cancer (mCRPC), according to Sun Pharma, the company commercializing the treatment.

The approval was based on findings from a phase II study comparing the Yonsa formulation of abiraterone acetate to the original, Zytiga, which was approved in 2011. In the trial, which was known as STAAR, Yonsa demonstrated therapeutic equivalence to Zytiga, based on serum testosterone levels, and both agents showed similar declines in PSA of ≥50% (PSA-50).

“We are pleased to add Yonsa to our growing oncology portfolio and continue to deliver on Sun Pharma’s commitment for enhanced patient access to innovative cancer therapies,” Abhay Gandhi, CEO - North America, Sun Pharma, said in a statement announcing the approval.

The Yonsa formulation of abiraterone acetate is developed to have a smaller overall particle size. In prior studies, the fine particle size was found to increase dissolution rates and oral bioavailability while decreasing the effects of food on treatment efficacy. In the phase II study, the 500-mg dose of Yonsa had similar absorption as the 1000-mg dose of Zytiga.

The STAAR trial included 53 patients with mCRPC who had not received prior abiraterone acetate, enzalutamide, radium-223, or chemotherapy (unless it was docetaxel ≥1 year prior to study entry). Patients were randomized in a 1:1 ratio to receive Yonsa at 500 mg (4 tablets at 125 mg each) or Zytiga at 1000 mg (4 tablets at 250 mg each). Yonsa was administered with methylprednisolone at 4 mg and Zytiga was given with prednisone at 5 mg.

Across both arms, approximately half of patients (54.7%) had Gleason >7 disease. There were more Caucasians in the Yonsa arm (83.3%) than in the Zytiga group (69%). The mean time since diagnosis of mCRPC was 2.1 years in both groups and baseline testosterone levels were 7.28 in the Yonsa group and 7.95 in the Zytiga arm (8.4% relative difference).

The mean testosterone level at day 9 and 10 was 0.32 (±0.45) in the Yonsa group and 0.29 (±0.29) in the Zytiga arm. The median level at day 9 and 10 was 0.15 with Yonsa and 0.19 with Zytiga. At day 28, patients in both arms had a mean testosterone level of 0.10 and the mean was 0.22 (±0.26) and 0.25 (±0.30) in the Yonsa and Zytiga groups, respectively. At day 84, the median was 0.10 with Yonsa and 0.15 with Zytiga.

PSA-50 was observed in more than 65% of patients in both arms of the study. The least square mean difference in serum PSA level between Yonsa and Zytiga at day 28 was -15.13 (P = .3642). At day 84, the difference was -18.80 (P = .4200).

Overall, fewer patients experienced treatment-emergent adverse events (AEs) in the Yonsa arm compared with Zytiga (75% vs 82.8%, respectively). Grade ≥3 AEs were experienced by 16.7% of patients in the Yonsa arm and for 17.2% in the Zytiga group. Four patients had a serious AE in the Yonsa group compared with 7 in the Zytiga arm, two of which led to death (prostate cancer progression and myocardial infarction).

Abiraterone acetate (Zytiga) was initially approved as a treatment for men with mCRPC following chemotherapy. It subsequently gained approval for use prior to chemotherapy. In February 2018, Zytiga was approved in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer.

Stein CA, Levin R, Given R, et al. Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study. Urol Oncol. 2018;36(2):81e9-81.e16.