Johnson & Johnson seeks EMA approval to expand AKEEGA use for HRR-altered prostate cancer patients

In a key move to expand its oncology portfolio in Europe, Johnson & Johnson (NYSE: JNJ) has submitted an application to the European Medicines Agency (EMA) seeking to extend the indication of AKEEGA—its dual-action tablet combining niraparib and abiraterone acetate—to include treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) characterized by homologous recombination repair (HRR) gene alterations. The proposed expansion builds on promising data from the pivotal Phase 3 AMPLITUDE study.

AKEEGA is already approved in multiple global markets, including the European Economic Area and the United States, for the treatment of BRCA1/2-mutated metastatic castration-resistant prostate cancer (mCRPC). This new application aims to extend its reach to a broader, yet biologically distinct, patient group whose disease remains responsive to hormone therapy but carries a poorer prognosis due to genetic mutations that impair DNA repair.

Why is Johnson & Johnson targeting HRR-altered mHSPC with an expanded AKEEGA indication in Europe?

The expanded indication request reflects a strategic focus on high-risk prostate cancer subtypes—particularly those with BRCA1/2 and other HRR gene alterations, which are present in over 20 percent of patients with mHSPC. These mutations are known to accelerate disease progression and reduce response durability. The European submission, led by Janssen-Cilag International NV (a Johnson & Johnson company), proposes the use of AKEEGA in combination with prednisone or prednisolone to significantly delay radiographic progression and symptomatic worsening, based on statistically significant outcomes observed in the AMPLITUDE study.

Institutional investors and oncology observers view the move as a calculated step toward defining a new standard of care for genetically predisposed patients whose treatment options are currently limited. Johnson & Johnson’s emphasis on precision medicine appears aligned with ongoing regulatory and payer shifts favoring biomarker-driven therapies.

What does the AMPLITUDE study reveal about AKEEGA’s efficacy in this patient population?

AMPLITUDE (NCT04497844) is a Phase 3 randomized, double-blind, placebo-controlled study enrolling 696 patients across 32 countries. It assessed niraparib combined with abiraterone acetate and prednisone (AAP) against placebo plus AAP in patients with deleterious germline or somatic HRR gene-altered mHSPC.

The primary endpoint, radiographic progression-free survival (rPFS), showed a statistically and clinically significant benefit in the AKEEGA arm. A secondary endpoint—time to symptomatic progression—also improved, with early signals suggesting better overall survival compared to standard care. These data were presented as a late-breaking abstract (#LBA5006) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and featured in the Best of ASCO program, highlighting their perceived clinical impact.

AKEEGA represents the first successful demonstration of combining a poly (ADP-ribose) polymerase (PARP) inhibitor with an androgen receptor pathway inhibitor (ARPI) in this early metastatic setting. The positive results reinforce growing confidence in exploiting synthetic lethality principles for cancers driven by DNA repair deficiencies.

How does the safety profile of AKEEGA compare with existing treatments for advanced prostate cancer?

The safety profile observed in AMPLITUDE was consistent with prior studies of AKEEGA in mCRPC, supporting its tolerability in earlier-stage patients. The most common Grade 3 or 4 adverse events included anemia and hypertension, but treatment discontinuations due to side effects were minimal, suggesting manageable toxicity when appropriately monitored.

This favorable safety outcome is critical, given the long-term nature of treatment in hormone-sensitive stages. For oncologists and regulatory reviewers alike, the low dropout rate may bolster confidence in the feasibility of long-duration use.

What are the regulatory and commercial implications of this EMA submission for Johnson & Johnson?

If approved, the expanded label would allow Johnson & Johnson to position AKEEGA earlier in the prostate cancer treatment paradigm across Europe. This could significantly increase the addressable market and revenue potential, particularly in high-incidence countries like Germany, Italy, France, and the United Kingdom.

Moreover, the move would deepen Johnson & Johnson’s leadership in prostate cancer, already fortified by its androgen deprivation and immune-oncology strategies. Analysts believe this label expansion, if granted, may also pave the way for similar submissions in the U.S., Canada, and Asia-Pacific markets where HRR testing is becoming standard practice.

Janssen’s global rights to niraparib in prostate cancer were secured through a 2016 collaboration and license agreement with TESARO, Inc. (now part of GSK), excluding Japan. Since then, Johnson & Johnson has positioned itself as a central player in developing combination regimens tailored to biomarker-defined cancer subtypes.

How does the biology of HRR-altered mHSPC contribute to treatment complexity and unmet needs?

Metastatic hormone-sensitive prostate cancer (also known as metastatic castration-sensitive prostate cancer) remains responsive to androgen deprivation therapy (ADT), but patients with HRR alterations often face faster disease progression and earlier onset of symptoms. These mutations impair the cancer cells’ ability to repair DNA, making them particularly susceptible to PARP inhibition but also resistant to traditional monotherapies.

As a result, the dual-mechanism approach of AKEEGA—simultaneously targeting AR signaling and DNA repair pathways—offers a rational and targeted strategy. By intervening before the disease evolves into the incurable mCRPC stage, Johnson & Johnson hopes to extend survival and improve quality of life.

This reflects a broader industry trend in oncology toward earlier intervention using genomically informed therapy.

What is the outlook for AKEEGA’s broader adoption and future research in prostate cancer?

Assuming a positive regulatory outcome in Europe, Johnson & Johnson is expected to push forward with further clinical development of AKEEGA combinations in other hormone-sensitive and castration-resistant settings, possibly even moving into earlier stages such as high-risk localized disease.

Future studies may explore triple combinations with immune checkpoint inhibitors or next-generation AR inhibitors to deepen response and delay resistance. Additionally, real-world data from post-approval use in mCRPC could inform further label refinements and payer negotiations.

Institutional sentiment remains cautiously optimistic, with attention now turning to how European regulators weigh the benefit-risk ratio in a pre-chemo, biomarker-selected population. The EMA review will also serve as a bellwether for companion diagnostic integration, access frameworks, and subsequent reimbursement decisions across national health systems.