J&J's Akeega Shows Promise in Earlier-Stage Prostate Cancer, Expanding PARP Inhibitor Potential

Johnson & Johnson's combination drug Akeega has demonstrated significant efficacy in treating earlier-stage prostate cancer patients with specific genetic mutations, according to new data presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. The results from the Phase 3 Amplitude trial suggest a potential expansion of PARP inhibitor use in prostate cancer treatment, particularly for patients with BRCA mutations.

Akeega's Performance in Earlier-Stage Prostate Cancer

Akeega, a combination of the PARP inhibitor niraparib (Zejula) and abiraterone acetate (Zytiga), showed promising results in men with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene mutations. The drug significantly reduced the risk of disease progression or death by 37% compared to Zytiga and prednisone alone in the overall HRR-mutated population.

The benefit was even more pronounced in patients with BRCA mutations, where Akeega reduced the risk of radiographic progression by 48%. Additionally, the combination therapy decreased the risk of symptomatic progression by 56% in BRCA-positive participants.

Lead study author Gerhardt Attard, M.D., Ph.D., from University College London, emphasized the importance of these findings, stating, "The challenge is that when we use PARP inhibitors as monotherapy at the end of the treatment sequence, resistance rapidly develops, and the median time to radiographic progression-free survival is shorter than 12 months. This group of patients have poor outcomes, significantly worse outcomes than other patients."

Regulatory Implications and Future Directions

While Akeega is currently approved only for BRCA-mutated, castration-resistant prostate cancer, these results could potentially lead to an expanded indication. Mark Wildgust, J&J's global medical affairs vice president for oncology, indicated that discussions with the FDA regarding a possible expansion to the broader HRR-mutated population are forthcoming.

However, the path forward for non-BRCA HRR mutations remains less clear. The benefit in this subgroup, which accounts for 45% of the Amplitude trial population, was more modest at around 20% improvement. Wildgust noted that while there is efficacy in the non-BRCA subgroup, it is heterogeneous and comprises several smaller gene subgroups.

The FDA has previously scrutinized the benefit of PARP inhibitors in non-BRCA HRR mutations, as evidenced by their decision to approve Akeega only for BRCA-mutated patients in the castration-resistant setting. This precedent suggests that regulatory approval for the broader HRR population in earlier-stage disease may face challenges.

Bradley McGregor, a genitourinary specialist at Dana-Farber Cancer Institute, commented on the study's implications, saying, "This data is quite compelling for the BRCA 1/2 patients where that magnitude of benefit is higher." He also emphasized the importance of genetic testing to identify patients most likely to benefit from PARP inhibitor treatment.

As the pharmaceutical industry continues to explore the potential of PARP inhibitors in prostate cancer, these results from the Amplitude trial represent a significant step forward in understanding their role in earlier-stage disease and highlight the importance of personalized treatment approaches based on genetic profiling.