Niraparib
- Generic Name
- Niraparib
- Brand Names
- Zejula
- Drug Type
- Small Molecule
- Chemical Formula
- C19H20N4O
- CAS Number
- 1038915-60-4
- Unique Ingredient Identifier
- HMC2H89N35
- Background
Niraparib is an orally active poly (ADP-ribose) polymerase (PARP) inhibitor. By blocking the enzymes responsible for DNA repair, niraparib induces cytotoxicity in cancer cells. Niraparib is selective towards PARP-1 and PARP-2. First approved by the FDA on March 27, 2017, niraparib is used to treat epithelial ovarian, fallopian tube, or primary peritoneal cancer. Niraparib was approved by the European Commission on November 16, 2017 and by Health Canada on June 27, 2019.
- Indication
Niraparib is indicated for the maintenance treatment of adult patients with advanced or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.
In Canada and the US, niraparib is also available in a combination product with abiraterone, which is indicated with prednisone for the treatment of adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). In Canada, this combination product is also used with prednisolone and is reserved for patients who are asymptomatic or mildly symptomatic, and in whom chemotherapy is not clinically indicated.
- Associated Conditions
- Advanced Epithelial Ovarian Cancer, Advanced Primary Peritoneal Carcinoma, Metastatic Castration-Resistant Prostate Cancer (mCRPC), Recurrent Epithelial Ovarian Cancer, Recurrent Fallopian Tube Cancer, Recurrent Primary Peritoneal Cancer, Advanced Fallopian Tubes Cancer
- Associated Therapies
- Maintenance therapy
GSK's Zejula Shows Promising Results in Phase II Mesothelioma Trial with 27% Reduction in Disease Progression
• Phase II NERO study demonstrates GSK's Zejula (niraparib) reduced risk of disease progression or death by 27% in relapsed mesothelioma patients compared to standard care.
• Patients treated with the PARP inhibitor gained an average of 1.5 months of progression-free survival, representing a significant advancement for a patient population with limited treatment options and poor prognosis.
• University Hospital Southampton NHS Foundation Trust plans to launch SELECTmeso, a biomarker-driven Phase II platform trial to further personalize treatment approaches for mesothelioma patients.
Acrivon Therapeutics Appoints Renowned Oncologist Dr. Mansoor Raza Mirza as Chief Medical Officer to Lead Clinical Development
• Dr. Mansoor Raza Mirza, a globally recognized gynecologic oncology expert with extensive experience in registrational trials, joins Acrivon Therapeutics as Chief Medical Officer effective April 9, 2025.
• Dr. Mirza will lead clinical development of ACR-368, currently in Phase 2b registrational-intent trials for endometrial cancer, and ACR-2316, a WEE1/PKMYT1 inhibitor in Phase 1 studies for solid tumors.
• Acrivon's proprietary AP3 platform enables precision oncology through proteomics-based drug discovery and companion diagnostics to identify patients most likely to benefit from specific treatments.
Novel BCMA-Directed CAR T-Cell Therapy Shows Promising Efficacy in Relapsed/Refractory Multiple Myeloma and AL Amyloidosis
• A second-generation BCMA-directed CAR T-cell therapy, MDC-CAR-BCMA001, demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma and AL amyloidosis, achieving a 5/6 overall response rate with 4 complete responses.
• The novel therapy showed a favorable safety profile with manageable toxicity, including low incidence of severe cytokine release syndrome and no neurotoxicity, even in patients with significant organ dysfunction.
• These promising results have prompted further investigation through ongoing clinical trials, including CARLOTTA001 (NCT05836896) and the CLEAR AL trial, potentially offering new hope for difficult-to-treat hematologic malignancies.
GSK's Blenrep Secures UK Approval for Multiple Myeloma Treatment in Combination Therapy
• The UK's medicines regulatory body has approved GSK's Blenrep (belantamab mafodotin) in combination with other drugs for multiple myeloma patients whose first treatment failed or caused severe side effects.
• This approval marks a significant comeback for Blenrep, which was withdrawn from markets in 2022 after failing to outperform existing treatments when used as monotherapy.
• Clinical trials demonstrated Blenrep's combination therapy extended progression-free survival and overall survival compared to standard care regimens, including those based on Darzalex (daratumumab).
Tezepelumab Shows Remarkable 92% Reduction in Nasal Polyp Surgery Need in Phase 3 Trial
• Phase 3 WAYPOINT trial demonstrates tezepelumab significantly reduced nasal polyp severity and improved nasal congestion scores in patients with severe chronic rhinosinusitis with nasal polyps.
• The study showed a dramatic 92% reduction in the need for nasal polyp surgery or systemic corticosteroid treatment compared to placebo over 52 weeks.
• Patients receiving tezepelumab experienced significant improvements in multiple symptoms, including loss of smell and sino-nasal outcomes, with similar adverse event rates to placebo.
European Commission Approves GSK's Jemperli Plus Chemotherapy for Advanced Endometrial Cancer
• The European Commission has approved Jemperli (dostarlimab) in combination with chemotherapy for first-line treatment of advanced or recurrent endometrial cancer.
• The approval expands the indication to include patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors, representing approximately 75% of cases.
• The RUBY trial demonstrated a 31% reduction in the risk of death with Jemperli plus chemotherapy compared to chemotherapy alone, with a median OS of 44.6 months.
• Jemperli, a PD-1 blocking antibody, is now an approved immuno-oncology-based treatment option for all patients with advanced endometrial cancer in the EU.
Drug Toxicity Leads to Early Discontinuation of Niraparib in Ovarian Cancer Treatment
A recent study highlights drug toxicity as the primary reason for early discontinuation of niraparib, a PARP inhibitor, in patients with epithelial ovarian cancer. The CHAR1ZMA study underscores the importance of individualized starting doses and dose modifications to manage toxicity effectively, aiming to prolong treatment duration and maximize therapeutic benefits.
Zai Lab's Tivdak Shows Positive Results in China Subpopulation of Phase 3 Cervical Cancer Trial
• Zai Lab's Tivdak demonstrated a 45% reduction in the risk of death compared to chemotherapy in Chinese patients with recurrent or metastatic cervical cancer.
• The China subpopulation results from the innovaTV 301 trial were consistent with global results, showing improved overall survival, PFS, and ORR.
• Zai Lab plans to submit a New Drug Application to China’s National Medical Products Administration in the first quarter of 2025.
• Tisotumab vedotin offers hope for addressing the unmet need for effective treatments after relapse, including after anti-PD(L)1 therapy.
Tisotumab Vedotin Demonstrates Survival Benefit in Chinese Cervical Cancer Subpopulation
• Tisotumab vedotin significantly improved overall survival compared to chemotherapy in Chinese patients with previously treated recurrent or metastatic cervical cancer.
• The antibody-drug conjugate reduced the risk of death by 45% in the Chinese subpopulation, consistent with global trial results.
• Zai Lab plans to submit a new drug application to China's National Medical Products Administration based on these findings.
• The results offer hope for addressing the unmet need for effective treatments after relapse, including after anti-PD-(L)1 therapy.
Tesaro's Niraparib Approved for Ovarian Cancer Maintenance Therapy
Tesaro's niraparib, marketed as Zejula, has been approved in the US for maintenance therapy in ovarian cancer, marking a significant step forward despite setbacks in breast cancer trials. The drug, a PARP inhibitor, is expected to generate substantial sales and is being developed for various other uses.
GSK's PARP Drug Zejula Approved for Wider Ovarian Cancer Population
The FDA has approved GSK's Zejula (niraparib) for a broader group of ovarian cancer patients, including those without the BRCA mutation, marking a significant expansion in the use of PARP inhibitors.
New Hope for Fibrolamellar Carcinoma: SUMMIT Trial Findings
The SUMMIT trial (NCT01953926) evaluated neratinib combined with pembrolizumab for fibrolamellar carcinoma, showing a 5% response rate and 13.3% disease control rate with single-agent therapy, and achieving partial responses in combination therapy. Patients tolerated the therapy well, despite grade 3 and 4 adverse events in two-thirds of patients.
Niraparib and Dostarlimab Show Promise in BRCA-Mutated, ER-Positive, HER2-Negative Breast Cancer
• A phase 2 trial (TBCRC-056) evaluated neoadjuvant niraparib plus dostarlimab in patients with germline BRCA-mutated, ER-positive, HER2-negative breast cancer, showing promising responses.
• The pathological complete response (pCR) rate was 16.7%, and 44.4% of patients achieved a residual cancer burden (RCB) score of zero or 1, indicating a substantial reduction in cancer burden.
• The combination therapy was generally well-tolerated, with the most common grade 3 treatment-related side effects being rash (27.8%) and increased alanine transaminase levels (16.7%).
GSK's Jemperli and Zejula Combo Shows Promise in Advanced Ovarian Cancer
• The FIRST-ENGOT-OV44 phase III trial of Jemperli (dostarlimab) combined with Zejula (niraparib) met its primary endpoint, improving progression-free survival (PFS) in advanced ovarian cancer.
• The addition of dostarlimab to standard chemotherapy and niraparib maintenance demonstrated a statistically significant difference in PFS compared to the comparator arm.
• While PFS improved, the key secondary endpoint of overall survival (OS) did not reach statistical significance, and further analyses are underway.
• The safety and tolerability profile of the combination therapy were consistent with the known profiles of the individual agents, according to GSK.
GSK's GSK'227 Receives FDA Breakthrough Therapy Designation for Relapsed Osteosarcoma
• The FDA granted Breakthrough Therapy Designation to GSK'227 for relapsed or refractory osteosarcoma after two prior lines of therapy.
• The designation aims to expedite the development of GSK'227, a B7-H3-targeted antibody-drug conjugate, for this rare bone cancer.
• The FDA's decision was based on promising data from the ARTEMIS-002 trial, which evaluated GSK'227 in osteosarcoma patients.
• GSK'227 represents a potential new treatment option for osteosarcoma patients with limited alternatives after chemotherapy failure.
ZEST Trial Halted Due to Low ctDNA Detection Rates in Early Breast Cancer
• The Phase III ZEST trial, evaluating niraparib for preventing breast cancer recurrence based on circulating tumor DNA (ctDNA), was terminated early due to low ctDNA detection rates.
• Broad entry criteria in ZEST led to the inclusion of low-risk patients, resulting in a low rate of ctDNA positivity and hindering the trial's randomization process.
• Exploratory analysis suggested a longer recurrence-free interval with niraparib in patients with low ctDNA levels at baseline, though the study was underpowered.
• Future ctDNA-guided trials should focus on higher-risk patients and earlier ctDNA testing during neoadjuvant therapy to improve feasibility and outcomes.
Olaparib Shows Sustained Benefit in Early-Stage BRCA-Mutated Breast Cancer
• Olaparib improves long-term survival in women with high-risk, early-stage breast cancer and BRCA1/2 mutations, reducing cancer recurrence risk by 35%.
• After six years, 87.5% of olaparib-treated patients were alive, compared to 83.2% in the placebo group, demonstrating a significant survival advantage.
• The OlympiA trial reinforces the importance of BRCA testing to identify patients who can benefit from personalized olaparib treatment early.
• Olaparib is now recommended by NICE in England and Wales for early-stage, high-risk breast cancer with BRCA1/2 mutations, improving survival chances.
Keytruda/Lenvima Combo Shows Mixed Results in Gastroesophageal Adenocarcinoma Trial
• The Phase 3 LEAP-015 trial evaluated Keytruda plus Lenvima with chemotherapy for HER2-negative gastroesophageal adenocarcinoma.
• The combination significantly improved progression-free survival and objective response rate compared to chemotherapy alone.
• However, the trial failed to meet its other primary endpoint of overall survival in the final analysis.
• The safety profile of the Keytruda plus Lenvima regimen was consistent with prior studies.
Niraparib Shows Promise in Extending Progression-Free Survival in Epithelial Ovarian Cancer
• Niraparib monotherapy extends real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) in patients with epithelial ovarian cancer (EOC).
• Patients with homologous recombination-deficient (HRd) tumors, particularly those with BRCA-mutated tumors, experienced longer rwPFS and rwTTNT.
• Niraparib demonstrates clinical benefit in stage III EOC patients with no visible residual disease (NVRD) after primary cytoreductive surgery (PCS).
• Niraparib stands out among PARP inhibitors for its broad frontline maintenance therapy approval in EOC, regardless of BRCA mutation or HRD status.
Zai Lab Reports Strong Q3 2024 Growth, Highlights Pipeline Advances Including KarXT and ZL-1310
• Zai Lab's Q3 2024 net product revenue reached $101.8 million, a 47% year-over-year increase, driven by VYVGART, ZEJULA, and NUZYRA sales.
• A China bridging study of KarXT in schizophrenia showed positive results, with regulatory submission expected in early 2025, potentially expanding treatment options.
• Phase 1 data for ZL-1310, a DLL3-targeted ADC for extensive-stage SCLC, demonstrated promising antitumor activity, suggesting best-in-class potential.
• The company anticipates launching three products in mainland China by the end of 2024 and aims for up to four regulatory submissions to the NMPA in the next six months.
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