J&J’s Akeega FDA approval to heat up PARP battle with dual-action treatment for prostate cancer:  GlobalData

The FDA recently granted approval for Johnson & Johnson’s (J&J) Akeega, a novel first-in-class combination tablet treatment for adults with breast cancer gene (BRCA)-positive, metastatic castration-resistant prostate cancer (mCRPC). Akeega’s current predicted sales will experience only a slight increase as a result of its narrow label and fierce competition with other recently approved poly(ADP-ribose) polymerase (PARP) inhibitors, according to GlobalData.

The approval was based on the Phase III MAGNITUDE study, which evaluated the combination therapy of PARP inhibitor Zejula and androgen biosynthesis inhibitor Zytiga boasting positive results of a 47 per cent risk reduction for radiographic progression-free survival (rPFS) in BRCA-positive patients. In the indication, Akeega joins the ranks of fellow PARP inhibitors, AstraZeneca/Merck’s Lynparza and Pfizer’s Talzenna. Based on GlobalData’s analyst consensus forecast, global combined annual sales of Zejula and Zytiga will reach $2.5 billion by 2029. However, only a small subset of these sales will be attributed to Akeega, as most of the sales will come from respective individual drugs’ sales in other marketed indications.

Jasminemay Barcelon, Oncology & Hematology Analyst at GlobalData comments, “Co-inhibition of PARP and androgen biosynthesis has shown a high level of activity in mCRPC associated with a deleterious BRCA mutation, as evidenced by a successful trend of approvals for recent PARP inhibitor and hormonal therapy combination treatments. This combination holds significant potential to improve outcomes for this patient population. Akeega has combined the inhibitory mechanisms of Zejula and Zytiga into an attractive dual-action single tablet for oral use.”

However, Akeega faces a challenge in the PARP inhibitor battle. Despite an impressive Phase III clinical trial reaching FDA approval in the front-line setting, the label is restrictive, with an indication only in BRCA-mutated mCRPC requiring a confirmed BRCA mutation via the FDA-approved companion diagnostics. Additionally, other competing PARP inhibitors with broader labels and increased efficacy have been approved in the past year for mCRPC, posing as strong contenders for physicians’ choice.

Barcelon continues, “AstraZeneca and Merck’s Lynparza/Zytiga combination was granted a similar narrow FDA label for patients with BRCA-mutated tumors. However, the combination presents with potentially higher efficacy than Akeega. The strongest rival is Talzenna in combination with Xtandi, which enjoys the advantage of a broader label encompassing all patients with homologous recombination repair mutated mCRPC.”

J&J is attempting to overcome Akeega’s constrictive label with the ongoing Phase III AMPLITUDE study targeting gene-mutated metastatic castration-sensitive prostate cancer (mCSPC) but finds itself in another competition with Pfizer. Talzenna is currently undergoing the Phase III TALAPRO-3 trial for the same mCRPC population associated with DNA damage repair gene mutations. The Lynparza/Zytiga combination is also under continued investigation for the China cohort in a Phase III study as first-line therapy for mCRPC patients.

Barcelon concludes, “Talzenna will enjoy its position as a leading PARP inhibitor with a higher patient share and competitive advantage in the gene-mutated mCRPC setting, as a broader approval across PARP inhibitors remains uncertain. Significant opportunity remains for agents seeking to secure an even wider label in mCRPC regardless of genetic mutation status.”