Niraparib/abiraterone acetate

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Niraparib/abiraterone acetate
Combination of
Niraparib Antineoplastic agent
Abiraterone acetate Hormone antagonist
Clinical data
Trade names Akeega
License data
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Identifiers
KEGG

Niraparib/abiraterone acetate, sold under the brand name Akeega, is a fixed-dose combination anti-cancer medication used for the treatment of prostate cancer. [2] It contains niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (antineoplastic agent), and abiraterone acetate, a CYP17 inhibitor (hormone antagonist). [2]

Contents

The most common side effects include anemia (low levels of red blood cells), high blood pressure, constipation, tiredness, nausea, thrombocytopenia (low levels of blood platelets), difficulty breathing, back pain, reduced appetite, neutropenia (low levels of neutrophils, a type of white blood cell), joint pain, vomiting, low levels of potassium, dizziness, difficulty sleeping, high blood glucose levels, and urinary tract infection. [2] [3]

Niraparib/abiraterone acetate was approved for medical use in the European Union in April 2023, [2] and in the United States in August 2023. [1] [3] [4]

Medical uses

In the European Union, niraparib/abiraterone is indicated for the treatment of adults with prostate cancer. [2] It is for people who have genetic mutations known as BRCA 1/2 mutations and who cannot have chemotherapy. [2] It is used in combination with prednisolone or another medicine prednisone, which is converted into prednisolone. [2]

In the United States, niraparib/abiraterone is indicated, in combination with prednisone, for adults with deleterious or suspected deleterious BRCA-mutated castration-resistant prostate cancer, as determined by an FDA-approved test. [1] [3]

History

Efficacy was evaluated in cohort 1 of MAGNITUDE (NCT03748641), a randomized, double-blind, placebo-controlled trial enrolling 423 participants with homologous recombination repair (HRR) gene-mutated mCRPC. [3] Participants were randomized (1:1) to receive niraparib 200 mg and abiraterone acetate 1,000 mg plus prednisone 10 mg daily or placebo and abiraterone acetate plus prednisone daily. [3] Participants were required to have a prior orchiectomy or be receiving gonadotropin-releasing hormone (GnRH) analogues. [3] Participants with mCRPC were eligible if they had not received prior systemic therapy in the mCRPC setting except for a short duration of prior abiraterone acetate plus prednisone (up to four months) and ongoing ADT. [3] Participants could have received prior docetaxel or androgen-receptor (AR) targeted therapies in earlier disease settings. [3] Randomization was stratified by prior docetaxel, prior AR targeted therapy, prior abiraterone acetate plus prednisone, and BRCA status. [3] Of the 423 participants enrolled, 225 (53%) had prospectively determined BRCA gene mutations (BRCAm). [3] No benefit was observed in mCRPC participants without an HRR gene mutation (Cohort 2 of MAGNITUDE) as the criterion for futility was met. [3]

Society and culture

On 23 February 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Akeega, intended for the treatment of adults with metastatic castration-resistant prostate cancer with BRCA 1/BRCA 2 mutations. [5] The applicant for this medicinal product is Janssen-Cilag International N.V. [5] [6] Niraparib/abiraterone acetate was approved for medical use in the European Union in April 2023. [2] It was approved for use in the United States in August 2023, based on the Phase 3 MAGNITUDE study. [3] [4]

Related Research Articles

<span class="mw-page-title-main">Prostate cancer</span> Male reproductive organ cancer

Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Early prostate cancer causes no symptoms. Most cases are detected after screening tests – typically blood tests for levels of prostate-specific antigen (PSA) – indicate unusual growth of prostate tissue. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score, with a higher score representing a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. Higher stage signifies a more advanced, more dangerous disease.

Nicholas J. Vogelzang was a medical oncologist with Comprehensive Cancer Centers of Nevada (CCCN). He serves as medical director of the Research Executive Committee and Associate Chair of the Developmental Therapeutics and Genitourinary Committees for US Oncology Research. His research interests include clinical trials for genitourinary malignancies and mesothelioma.

<span class="mw-page-title-main">Satraplatin</span> Chemical compound

Satraplatin is a platinum-based antineoplastic agent that was under investigation as a treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.

<span class="mw-page-title-main">Abiraterone acetate</span> Chemical compound

Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth.

<span class="mw-page-title-main">Enzalutamide</span> Antiandrogen medication used in treatment of prostate cancer

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Radium-223 is an isotope of radium with an 11.4-day half-life. It was discovered in 1905 by T. Godlewski, a Polish chemist from Kraków, and was historically known as actinium X (AcX). Radium-223 dichloride is an alpha particle-emitting radiotherapy drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover. The principal use of radium-223, as a radiopharmaceutical to treat metastatic cancers in bone, takes advantage of its chemical similarity to calcium, and the short range of the alpha radiation it emits.

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

<span class="mw-page-title-main">Veliparib</span> Chemical compound

Veliparib (ABT-888) is a potential anti-cancer drug acting as a PARP inhibitor. It kills cancer cells by blocking a protein called PARP, thereby preventing the repair of DNA or genetic damage in cancer cells and possibly making them more susceptible to anticancer treatments. Veliparib may make whole brain radiation treatment work more effectively against brain metastases from NSCLC. It has been shown to potentiate the effects of many chemotherapeutics, and as such has been part of many combination clinical trials.

<span class="mw-page-title-main">Cabazitaxel</span> Chemical compound

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Galeterone is a steroidal antiandrogen which was under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique triple mechanism of action, acting as an androgen receptor antagonist, androgen receptor down regulator, and CYP17A1 inhibitor, the latter of which prevents the biosynthesis of androgens. As a CYP17A1 inhibitor, galeterone shows selectivity for 17,20-lyase over 17α-hydroxylase.

<span class="mw-page-title-main">Seviteronel</span> Chemical compound

Seviteronel is an experimental cancer medication which is under development by Viamet Pharmaceuticals and Innocrin Pharmaceuticals for the treatment of prostate cancer and breast cancer. It is a nonsteroidal CYP17A1 inhibitor and works by inhibiting the production of androgens and estrogens in the body. As of July 2017, seviteronel is in phase II clinical trials for both prostate cancer and breast cancer. In January 2016, it was designated fast-track status by the United States Food and Drug Administration for prostate cancer. In April 2017, seviteronel received fast-track designation for breast cancer as well.

<span class="mw-page-title-main">Apalutamide</span> Chemical compound

Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC). It is taken by mouth.

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References

  1. 1 2 3 "Akeega- niraparib tosylate monohydrate and abiraterone acetate tablet, film coated". DailyMed. 22 August 2023. Archived from the original on 24 August 2023. Retrieved 23 August 2023.
  2. 1 2 3 4 5 6 7 8 9 "Akeega EPAR". European Medicines Agency. 2 June 2023. Archived from the original on 3 June 2023. Retrieved 2 June 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves niraparib and abiraterone acetate plus prednisone for BRCA-mutated metastatic castration-resistant prostate cancer". U.S. Food and Drug Administration (FDA). 11 August 2023. Retrieved 6 September 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. 1 2 "U.S. FDA Approves Akeega (Niraparib and Abiraterone Acetate), the First-And-Only Dual Action Tablet for the Treatment of Patients with BRCA-Positive Metastatic Castration-Resistant Prostate Cancer" (Press release). Janssen. 11 August 2023. Retrieved 17 August 2023 via PR Newswire.
  5. 1 2 "Akeega: Pending EC decision". European Medicines Agency (EMA). 24 February 2023. Archived from the original on 25 February 2023. Retrieved 24 February 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. "Janssen Receives Positive CHMP Opinion for Akeega (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone for the Treatment of Adult Patients with BRCA1/2 Gene-Mutated Metastatic Castration Resistant Prostate Cancer" (Press release). Janssen Pharmaceutica NV. 24 February 2023. Archived from the original on 25 February 2023. Retrieved 24 February 2023 via GlobeNewswire.