Approval is based on the Phase 3 MAGNITUDE study, a prospectively designed precision medicine study including the largest population of BRCA-positive patients in combination trials to date with metastatic castration-resistant prostate cancer (mCRPC)
AKEEGA™ plus prednisone significantly improved radiographic progression-free survival compared to abiraterone acetate plus prednisone (AAP) in patients with BRCA-positive mCRPC
HORSHAM, PA, USA I August 11, 2023 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food & Drug Administration (FDA) has approved AKEEGA™ (niraparib and abiraterone acetate), the first-and-only dual action tablet combining a PARP inhibitor with abiraterone acetate, given with prednisone, for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive mCRPC, as detected by an FDA-approved test.1
“As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation,” said Kim Chi, M.D.*, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the Phase 3 MAGNITUDE study. “We prospectively designed the MAGNITUDE study to identify the subset of patients most likely to benefit from targeted treatment with AKEEGA and to help us understand how we can potentially achieve better health outcomes for patients.”
Prostate cancer is one of the most common cancers in the U.S., with an estimated 288,300 new cases and nearly 35,000 deaths expected in 2023.2 Approximately 10 to 15 percent of patients with mCRPC have BRCA gene alterations. Patients with BRCA-positive mCRPC are more likely to have aggressive disease and may experience poor outcomes and a shorter survival time.3,4,5,6,7
“The approval of AKEEGA brings an important treatment option to patients with prostate cancer as they consider their road ahead, and it also highlights the importance of genetic testing and precision medicine for this disease,” said Shelby Moneer, MS, CHES**, Vice President of Patient Programs and Education, ZERO Prostate Cancer. “All individuals diagnosed with prostate cancer should consider genetic testing, especially those from racial and ethnic minority groups who tend to have worse cancer outcomes. This is imperative to close the racial and ethnic disparities in prostate cancer health outcomes.”
The FDA approval is based on positive results from the randomized, double-blind, placebo-controlled multi-center Phase 3 MAGNITUDE study. In BRCA-positive patients treated with the combination AKEEGA™ plus prednisone, a statistically significant 47 percent risk reduction was observed for radiographic progression-free survival (rPFS) (Hazard ratio [HR], 0.53; p=0.001). At the second interim analysis (IA2), with median follow-up at 24.8 months in the BRCA-positive subgroup, rPFS by central review demonstrated a consistent trend favoring AKEEGA™ plus prednisone, with a median rPFS of 19.5 months compared with 10.9 months for placebo and AAP (HR, 0.55 [95 percent confidence interval (CI), 0.39-0.78]). Additionally, there was an observed improvement in the secondary endpoints of time to symptomatic progression (TSP) (HR, 0.54 [95 percent CI, 0.35-0.85]) and time to initiation of cytotoxic chemotherapy (TCC) (HR, 0.56 [95 percent CI, 0.35-0.90]) for AKEEGA™ plus prednisone compared with AAP alone, supported by a trend towards improvement in overall survival (OS) (HR, 0.88 [95 percent CI, 0.58-1.34]).
The observed safety profile of the combination of AKEEGA™ plus prednisone was consistent with the known safety profile of each FDA-approved monotherapy. Of the patients in the MAGNITUDE study with a BRCA gene alteration, 41 percent who received AKEEGA™ experienced a serious adverse event (AE). The most common AEs occurring in 20 percent or more of patients who received AKEEGA™ plus prednisone versus patients who received placebo and AAP were musculoskeletal pain (44 percent vs. 42 percent, respectively), fatigue (43 percent vs. 30 percent), constipation (34 percent vs. 20 percent), hypertension (33 percent vs. 27 percent) and nausea (33 percent vs. 21 percent). Permanent discontinuation of any component of AKEEGA™ due to an adverse reaction occurred in 15 percent of patients.
“Janssen’s legacy of advancing the science of prostate cancer has contributed to the evolution of transformational treatment approaches for more than a decade,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “This milestone, which marks the approval of Janssen’s third prostate cancer treatment, highlights the importance of advancing precision medicine approaches and genetic testing for the treatment of patients with BRCA-positive mCRPC.”
About AKEEGA™
AKEEGA™ (niraparib and abiraterone acetate) is the first-and-only orally administered, once daily dual action tablet (DAT) of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, an androgen biosynthesis inhibitor. The novel DAT combination therapy targets two oncogenic drivers in patients with mCRPC and HRR gene alterations. AKEEGA™ is indicated with prednisone for the treatment of adults with mCRPC and BRCA-positive mutations. The recommended starting dose is 200 mg niraparib/1,000 mg abiraterone acetate (two tablets). The 100 mg niraparib/1,000 mg abiraterone acetate dose option (two tablets) is available for dose reduction.
In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GlaxoSmithKline [GSK] in 2019) for exclusive rights to niraparib in prostate cancer.
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer characterizes cancer that no longer responds to androgen deprivation therapy and has spread to other parts of the body. The most common metastatic sites are bones, followed by lungs and liver. Prostate cancer is the second most common cancer in men worldwide, behind lung cancer. More than one million patients around the world are diagnosed with prostate cancer each year. Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.2,3,4,5
About MAGNITUDE
MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multi-center clinical study evaluating the safety and efficacy of the combination of AKEEGA™ plus prednisone for patients with mCRPC, with or without certain HRR gene alterations, and who have not received prior therapy for mCRPC except for up to four months of AAP.
The study included patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative), who were randomized 1:1 to receive niraparib 200 mg once daily plus AAP or placebo plus AAP.8 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations.9,10,11 The primary endpoint of the MAGNITUDE trial was rPFS assessed by blinded independent central review.12 Secondary endpoints included TCC, TSP and OS. Analysis of the group of patients with BRCA alterations was alpha controlled for rPFS and prespecified for other endpoints.
Access to AKEEGA™ (niraparib and abiraterone acetate)
Once a patient and their doctor have decided that AKEEGA™ is right for the patient, Janssen can help find the resources patients may need to get started and stay on therapy. Janssen offers support navigating the payer processes to assist patients in gaining access to AKEEGA™. We can provide information on insurance coverage and potential out-of-pocket costs and identify options that may help make AKEEGA™ more affordable. If patients have commercial or private health insurance and need help paying for AKEEGA™, the Janssen CarePath Savings Program may be able to help. To learn more about access and affordability support visit JanssenCarePath.com or call 1-877-CarePath (1-877-227-3728). We also offer personalized support for patients that provides one-on-one guidance, information, and educational resources, which includes helping them explore cost support options. Patients can get connected to dedicated support from our Care Navigators by calling Janssen Compass® directly at 844-628-1234 or by visiting JanssenCompass.com and requesting an introductory call. Janssen Compass® is limited to education for patients about their Janssen therapy, its administration, and/or their disease. It is intended to supplement a patient’s understanding of their therapy and is not intended to provide medical advice, replace a treatment plan from the patient’s doctor or nurse, provide case management services, or serve as a reason to prescribe a Janssen medication.
Please see the full Prescribing Information for AKEEGA™.
*Dr. Chi has been a paid consultant to Janssen; Dr. Chi has not been paid for any media work.
**Ms. Moneer has not been paid for any media work.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
1 AKEEGA Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
2 American Cancer Society. Cancer Facts & Figures 2023. Accessed May 11, 2023. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf
3 Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021 Aug 3;12(16):1600-1614. doi: 10.18632/oncotarget.28015. PMID: 34381565; PMCID: PMC8351605. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351605/
4 Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: A prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. doi:10.1200/JCO.18.00358.
5 Cavanagh, H., & Rogers, K. M. (2015). The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice, 13(1), 16. https://doi.org/10.1186/s13053-015-0038-x
6 Messina, C., Cattrini, C., Soldato, D., et al (2020). BRCA mutations in prostate cancer: Prognostic and predictive Implications. J Oncol., 2020, 4986365. https://doi.org/10.1155/2020/4986365
7 Na, R., Zheng, S. L., Han, M., et al (2017). Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. European Urology, 71(5), 740–747. https://doi.org/10.1016/j.eururo.2016.11.033
8 Chi et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Oral presentation, 2022 ASCO GU Annual Meeting.
9 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
10 Efstathiou E, et al. Niraparib With Abiraterone Acetate and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer and Homologous Recombination Repair Gene Alterations: Second Interim Analysis of MAGNITUDE. Poster presentation, 2023 ASCO GU Annual Meeting. February 16, 2023.
11 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
12 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
SOURCE: Janssen Pharmaceutical Companies of Johnson & Johnson
Post Views: 342
Approval is based on the Phase 3 MAGNITUDE study, a prospectively designed precision medicine study including the largest population of BRCA-positive patients in combination trials to date with metastatic castration-resistant prostate cancer (mCRPC)
AKEEGA™ plus prednisone significantly improved radiographic progression-free survival compared to abiraterone acetate plus prednisone (AAP) in patients with BRCA-positive mCRPC
HORSHAM, PA, USA I August 11, 2023 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food & Drug Administration (FDA) has approved AKEEGA™ (niraparib and abiraterone acetate), the first-and-only dual action tablet combining a PARP inhibitor with abiraterone acetate, given with prednisone, for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive mCRPC, as detected by an FDA-approved test.1
“As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation,” said Kim Chi, M.D.*, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the Phase 3 MAGNITUDE study. “We prospectively designed the MAGNITUDE study to identify the subset of patients most likely to benefit from targeted treatment with AKEEGA and to help us understand how we can potentially achieve better health outcomes for patients.”
Prostate cancer is one of the most common cancers in the U.S., with an estimated 288,300 new cases and nearly 35,000 deaths expected in 2023.2 Approximately 10 to 15 percent of patients with mCRPC have BRCA gene alterations. Patients with BRCA-positive mCRPC are more likely to have aggressive disease and may experience poor outcomes and a shorter survival time.3,4,5,6,7
“The approval of AKEEGA brings an important treatment option to patients with prostate cancer as they consider their road ahead, and it also highlights the importance of genetic testing and precision medicine for this disease,” said Shelby Moneer, MS, CHES**, Vice President of Patient Programs and Education, ZERO Prostate Cancer. “All individuals diagnosed with prostate cancer should consider genetic testing, especially those from racial and ethnic minority groups who tend to have worse cancer outcomes. This is imperative to close the racial and ethnic disparities in prostate cancer health outcomes.”
The FDA approval is based on positive results from the randomized, double-blind, placebo-controlled multi-center Phase 3 MAGNITUDE study. In BRCA-positive patients treated with the combination AKEEGA™ plus prednisone, a statistically significant 47 percent risk reduction was observed for radiographic progression-free survival (rPFS) (Hazard ratio [HR], 0.53; p=0.001). At the second interim analysis (IA2), with median follow-up at 24.8 months in the BRCA-positive subgroup, rPFS by central review demonstrated a consistent trend favoring AKEEGA™ plus prednisone, with a median rPFS of 19.5 months compared with 10.9 months for placebo and AAP (HR, 0.55 [95 percent confidence interval (CI), 0.39-0.78]). Additionally, there was an observed improvement in the secondary endpoints of time to symptomatic progression (TSP) (HR, 0.54 [95 percent CI, 0.35-0.85]) and time to initiation of cytotoxic chemotherapy (TCC) (HR, 0.56 [95 percent CI, 0.35-0.90]) for AKEEGA™ plus prednisone compared with AAP alone, supported by a trend towards improvement in overall survival (OS) (HR, 0.88 [95 percent CI, 0.58-1.34]).
The observed safety profile of the combination of AKEEGA™ plus prednisone was consistent with the known safety profile of each FDA-approved monotherapy. Of the patients in the MAGNITUDE study with a BRCA gene alteration, 41 percent who received AKEEGA™ experienced a serious adverse event (AE). The most common AEs occurring in 20 percent or more of patients who received AKEEGA™ plus prednisone versus patients who received placebo and AAP were musculoskeletal pain (44 percent vs. 42 percent, respectively), fatigue (43 percent vs. 30 percent), constipation (34 percent vs. 20 percent), hypertension (33 percent vs. 27 percent) and nausea (33 percent vs. 21 percent). Permanent discontinuation of any component of AKEEGA™ due to an adverse reaction occurred in 15 percent of patients.
“Janssen’s legacy of advancing the science of prostate cancer has contributed to the evolution of transformational treatment approaches for more than a decade,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “This milestone, which marks the approval of Janssen’s third prostate cancer treatment, highlights the importance of advancing precision medicine approaches and genetic testing for the treatment of patients with BRCA-positive mCRPC.”
About AKEEGA™
AKEEGA™ (niraparib and abiraterone acetate) is the first-and-only orally administered, once daily dual action tablet (DAT) of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, an androgen biosynthesis inhibitor. The novel DAT combination therapy targets two oncogenic drivers in patients with mCRPC and HRR gene alterations. AKEEGA™ is indicated with prednisone for the treatment of adults with mCRPC and BRCA-positive mutations. The recommended starting dose is 200 mg niraparib/1,000 mg abiraterone acetate (two tablets). The 100 mg niraparib/1,000 mg abiraterone acetate dose option (two tablets) is available for dose reduction.
In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GlaxoSmithKline [GSK] in 2019) for exclusive rights to niraparib in prostate cancer.
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer characterizes cancer that no longer responds to androgen deprivation therapy and has spread to other parts of the body. The most common metastatic sites are bones, followed by lungs and liver. Prostate cancer is the second most common cancer in men worldwide, behind lung cancer. More than one million patients around the world are diagnosed with prostate cancer each year. Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.2,3,4,5
About MAGNITUDE
MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multi-center clinical study evaluating the safety and efficacy of the combination of AKEEGA™ plus prednisone for patients with mCRPC, with or without certain HRR gene alterations, and who have not received prior therapy for mCRPC except for up to four months of AAP.
The study included patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative), who were randomized 1:1 to receive niraparib 200 mg once daily plus AAP or placebo plus AAP.8 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations.9,10,11 The primary endpoint of the MAGNITUDE trial was rPFS assessed by blinded independent central review.12 Secondary endpoints included TCC, TSP and OS. Analysis of the group of patients with BRCA alterations was alpha controlled for rPFS and prespecified for other endpoints.
Access to AKEEGA™ (niraparib and abiraterone acetate)
Once a patient and their doctor have decided that AKEEGA™ is right for the patient, Janssen can help find the resources patients may need to get started and stay on therapy. Janssen offers support navigating the payer processes to assist patients in gaining access to AKEEGA™. We can provide information on insurance coverage and potential out-of-pocket costs and identify options that may help make AKEEGA™ more affordable. If patients have commercial or private health insurance and need help paying for AKEEGA™, the Janssen CarePath Savings Program may be able to help. To learn more about access and affordability support visit JanssenCarePath.com or call 1-877-CarePath (1-877-227-3728). We also offer personalized support for patients that provides one-on-one guidance, information, and educational resources, which includes helping them explore cost support options. Patients can get connected to dedicated support from our Care Navigators by calling Janssen Compass® directly at 844-628-1234 or by visiting JanssenCompass.com and requesting an introductory call. Janssen Compass® is limited to education for patients about their Janssen therapy, its administration, and/or their disease. It is intended to supplement a patient’s understanding of their therapy and is not intended to provide medical advice, replace a treatment plan from the patient’s doctor or nurse, provide case management services, or serve as a reason to prescribe a Janssen medication.
Please see the full Prescribing Information for AKEEGA™.
*Dr. Chi has been a paid consultant to Janssen; Dr. Chi has not been paid for any media work.
**Ms. Moneer has not been paid for any media work.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
1 AKEEGA Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
2 American Cancer Society. Cancer Facts & Figures 2023. Accessed May 11, 2023. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf
3 Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021 Aug 3;12(16):1600-1614. doi: 10.18632/oncotarget.28015. PMID: 34381565; PMCID: PMC8351605. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351605/
4 Castro E, Romero-Laorden N, Del Pozo A, et al. PROREPAIR-B: A prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490-503. doi:10.1200/JCO.18.00358.
5 Cavanagh, H., & Rogers, K. M. (2015). The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice, 13(1), 16. https://doi.org/10.1186/s13053-015-0038-x
6 Messina, C., Cattrini, C., Soldato, D., et al (2020). BRCA mutations in prostate cancer: Prognostic and predictive Implications. J Oncol., 2020, 4986365. https://doi.org/10.1155/2020/4986365
7 Na, R., Zheng, S. L., Han, M., et al (2017). Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. European Urology, 71(5), 740–747. https://doi.org/10.1016/j.eururo.2016.11.033
8 Chi et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Oral presentation, 2022 ASCO GU Annual Meeting.
9 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
10 Efstathiou E, et al. Niraparib With Abiraterone Acetate and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer and Homologous Recombination Repair Gene Alterations: Second Interim Analysis of MAGNITUDE. Poster presentation, 2023 ASCO GU Annual Meeting. February 16, 2023.
11 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
12 AKEEGA™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
SOURCE: Janssen Pharmaceutical Companies of Johnson & Johnson
Post Views: 342
