Johnson & Johnson has announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its supplemental New Drug Application (sNDA) for AKEEGA (niraparib and abiraterone acetate dual-action tablet) combined with prednisone for patients with BRCA-mutated metastatic castration-sensitive prostate cancer (mCSPC). This patient group currently faces a poor prognosis and limited treatment options.
The sNDA submission is based on data from the Phase 3 AMPLITUDE study, which showed that AKEEGA plus prednisone reduced the risk of radiographic progression or death by 48 percent in patients with BRCA-mutated mCSPC. The study also found a significant 56 percent delay in time to symptomatic progression and a trend toward improved overall survival, with a 25 percent reduction in risk of death.
The AMPLITUDE study included 696 participants from 32 countries and evaluated the efficacy and safety of niraparib and abiraterone acetate in a dual-action tablet formulation, in combination with prednisone and androgen deprivation therapy (ADT). The most common severe adverse events in the treatment group were anemia and hypertension.
If approved, AKEEGA plus prednisone would become the first PARP-based precision medicine combination treatment for this population. Patients with BRCA-mutated mCSPC experience more rapid disease progression and shorter survival, underscoring the need for new targeted therapies and early genetic testing to inform treatment decisions.
Johnson & Johnson noted: “At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com.”
AKEEGA is already approved by the European Medicines Agency and received FDA Priority Review in August 2023 for treating BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). The therapy combines niraparib, a PARP inhibitor, and abiraterone acetate, a CYP17 inhibitor.
The company’s press release also contains detailed safety information about AKEEGA. Warnings include risks such as myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), myelosuppression (including anemia), hypokalemia, fluid retention, cardiovascular reactions such as hypertension, hepatotoxicity, adrenal insufficiency, hypoglycemia (particularly when used with certain diabetes medications), increased risk of fractures and mortality when combined with radium Ra 223 dichloride, posterior reversible encephalopathy syndrome (PRES), embryo-fetal toxicity, and potential fertility effects in males.
The most common adverse reactions reported included decreased hemoglobin levels, musculoskeletal pain, fatigue, hypertension, nausea, edema, infections such as COVID-19, arrhythmia, falls, among others. Fatal adverse reactions occurred in 9 percent of patients treated with AKEEGA during trials.
Drug interactions are also addressed; strong CYP3A4 inducers should be avoided as they may reduce abiraterone concentrations. AKEEGA may increase concentrations of CYP2D6 or CYP2C8 substrates.
Janssen Biotech, Inc., part of Johnson & Johnson companies, entered into an agreement in April 2016 with TESARO Inc., now part of GlaxoSmithKline (GSK), for exclusive rights to niraparib in prostate cancer outside Japan.
The press release concludes with cautionary statements about forward-looking statements related to product development and anticipated benefits of AKEEGA.
For more information about hormone-sensitive prostate cancer definitions and background on disease progression patterns to metastatic castration-resistant prostate cancer (mCRPC), reference information is available from the National Cancer Institute (https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hormone-sensitive-prostate-cancer).
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