Johnson & Johnson's Akeega is opening new fronts in prostate cancer treatment with a fresh FDA approval, making it the first precision medicine combo for patients with BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC).
Akeega, a dual-action tablet made up of J&J’s androgen-directed prostate cancer med Zytiga (abiraterone acetate) and the PARP inhibitor niraparib—sold by GSK as Zejula in other indications—is added to corticosteroid medication prednisone to delay disease progression of the aggressive form of prostate cancer.
J&J’s Amplitude study was the first showing that a PARP inhibitor-androgen receptor pathway inhibitor treatment combination could delay both radiographic and symptomatic disease progression in the disease type, Dana-Farber Cancer Institute’s Bradley McGregor, M.D., noted in a company press release.
In Amplitude, Akeega plus prednisone and androgen deprivation therapy (ADT) cut the risk of radiographic progression or death by 54% compared to an oral placebo and the current standard of care of Zytiga combined with prednisone and ADT. The combo therapy also extended the time to symptomatic progression by 59%, J&J said.
"This expanded indication for Akeega reflects our commitment to push the boundaries of science and deliver more personalized, effective treatment options across the prostate cancer continuum," the company’s head of solid tumors, U.S. medical affairs, Mahadi Baig, M.D., commented in the release.
About 25% of patients with mCSPC have HRR gene alternations, including BRCA, which is linked to faster disease progression and worse survival outcomes. Although the treatment landscape for prostate cancer has advanced in recent years, “almost all” patients eventually develop resistance to currently available therapies and many progress to the incurable stage, the company notes.
J&J’s Amplitude trial is an ongoing phase 3 study evaluating Akeega in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered mCSPC. At this year’s American Society of Clinical Oncology annual meeting, the company revealed that Akeega significantly reduced patients' risk of tumor progression or death by 37%.
However, the Akeega regimen’s magnitude of progression-free survival benefit was notably larger in the BRCA-mutated subgroup, suggesting that the benefit “may be greatest in patients with BRCA alterations,” lead study author Gerhardt Attard, M.D., Ph.D., from University College London, said during a press briefing at the time.
The FDA agreed in its approval release, pointing to an exploratory analysis that indicates “the overall improvement was primarily attributed to the results seen in patients with BRCA2m."
The limited approval echoes Akeega’s first nod in 2023 for BRCA-mutated metastatic castration-resistant prostate cancer—a later stage of the disease—and may speak to the wider struggles of the PARP drug class to extend beyond a niche subgroup of prostate cancer. AstraZeneca’s first-in-class Lynparza, for one, holds a narrowed BRCA-positive label in mCRPC when combined with Zytiga, while Pfizer’s own PARP Talzenna has a slightly broader indication that covers HRR gene mutations.
Still, Akeega’s new move into the earlier, castration-sensitive treatment stage is one that other PARPs have not matched, sharpening the prostate cancer edge that J&J is looking to bolster with its recent $3.03 billion acquisition of Halda Therapeutics and its early-stage mCRPC candidate HLD-0915.
The company has not yet reported individual Akeega sales figures, but collected $20.8 billion in 2024 oncology sales, including $631 million for 2011-approved Zytiga.