Last updated: June 27, 2026
Zejula (niraparib, MK-4827) is an oral, once-daily, selective PARP1/2 inhibitor originally discovered at Merck (MK-4827), licensed to Tesaro Inc. (which obtained the original FDA approval in 2017), and acquired by GSK (GlaxoSmithKline) through the Tesaro acquisition in December 2018. Janssen holds niraparib prostate cancer rights in certain territories. Zejula is the FDA-approved PARP inhibitor with the broadest within-disease regulatory footprint in ovarian cancer — it is the only PARP inhibitor approved for first-line ovarian cancer maintenance regardless of BRCA mutation or HRD status (PRIMA, April 2020). Dosed once daily orally (200 mg or 300 mg starting dose, individualized by baseline body weight and platelet count).
Mechanism of action:Niraparib selectively inhibits PARP1 and PARP2, two nuclear enzymes that mediate DNA single-strand break repair and the broader DNA damage response. By blocking PARP-mediated repair in tumors that already have defective homologous-recombination repair (BRCA1/2 mutations, HRD-positive tumors), niraparib exploits synthetic lethality: the cancer cell accumulates unrepairable DNA damage and undergoes apoptosis, while normal cells with intact HR repair are largely spared. Niraparib is also a PARP "trapper" — it stabilizes the PARP-DNA complex on chromatin, blocking replication forks — with intermediate trapping potency in the class (talazoparib > niraparib > olaparib ≈ rucaparib). See the PARP Inhibitors mechanism hub for the cross-drug class comparison.
Regulatory status:FDA-approved in 2 active indications, both in epithelial ovarian, fallopian tube, or primary peritoneal cancer: first-line maintenance regardless of biomarker status (PRIMA Phase 3 trial, April 29, 2020 — the broadest PARP indication of any FDA-approved PARPi) and recurrent maintenance after platinum response regardless of BRCA status (NOVA Phase 3 trial, March 27, 2017). A third indication (October 23, 2019) for HRD-positive heavily-pretreated recurrent ovarian based on the QUADRA trial was voluntarily withdrawn in 2023 after confirmatory data did not support continued accelerated approval.
PARP (poly ADP-ribose polymerase) is a family of enzymes that help cells repair single-strand breaks in DNA. PARP1 and PARP2 are the dominant cancer-relevant members. When PARP is inhibited, single-strand breaks persist and become double-strand breaks during the next round of DNA replication. Normal cells repair those double-strand breaks using the homologous recombination (HR) pathway — a high-fidelity repair system driven by BRCA1, BRCA2, PALB2, and the broader HRR gene panel. Cancers with defective HR (BRCA1/2 mutations, HRD-positive tumors) cannot accurately repair the double-strand breaks; they accumulate unrepairable damage and die. This is synthetic lethality — two individually survivable defects (PARP inhibition + HR deficiency) become lethal in combination.
Niraparib's distinguishing feature in the PARP class is the breadth of its FDA label in ovarian cancer. Other PARP inhibitors (olaparib, rucaparib, talazoparib) require a BRCA or HRR biomarker for FDA-approved use. Niraparib is the only PARP inhibitor approved for first-line ovarian cancer maintenance regardless of BRCA or HRD status — the PRIMA trial, FDA-approved April 2020. This matters in practice because many ovarian cancer patients do not yet have BRCA / HRD biomarker results at the moment their oncologist needs to make a maintenance-therapy decision, and many patients are HRD-negative or have unknown biomarker status. PRIMA showed PFS benefit across all biomarker subgroups — largest in HRD-positive, smallest in HRD-negative, but present in all — making niraparib uniquely positioned for the broadest 1L ovarian maintenance population.
Niraparib is also blood-brain-barrier-penetrant — documented in preclinical models and Phase 1/2 glioma studies — a pharmacology feature that distinguishes it within the PARP class. This BBB penetration is the rationale behind NCT06388733, the first PARP inhibitor Phase 3 in glioblastoma: niraparib vs temozolomide in newly-diagnosed MGMT-unmethylated GBM, the population that derives little benefit from TMZ because the MGMT enzyme actively repairs the DNA damage TMZ produces. If positive, the trial would replace temozolomide for a major newly-diagnosed GBM subgroup and expand the PARP class beyond ovarian / breast / mCRPC / pancreatic into brain tumors.
Zejula has 2 active FDA approvals, both in epithelial ovarian, fallopian tube, or primary peritoneal cancer, plus one withdrawn indication.
1L Advanced Ovarian Cancer Maintenance, Regardless of Biomarker Status (PRIMA)
Recurrent Ovarian Cancer Maintenance, Regardless of BRCA Status (NOVA)
HRD-Positive Heavily-Pretreated Recurrent Ovarian (QUADRA) — VOLUNTARILY WITHDRAWN 2023
★ The PRIMA All-Comers 1L Maintenance Differentiator
In ovarian cancer, the first-line maintenance decision is made shortly after a patient completes platinum-based induction chemotherapy. In real clinical practice, many patients do not yet have their BRCA / HRD biomarker results at that moment — germline BRCA testing turnaround can be days to weeks, somatic / HRD testing on tumor tissue can take longer, and a meaningful fraction of patients have HRD-negative or unknown biomarker status when the maintenance question is on the table.
Zejula is the only FDA-approved PARP inhibitor for 1L ovarian maintenance regardless of BRCA / HRD biomarker status. The PRIMA Phase 3 trial showed PFS benefit across all biomarker subgroups: largest in HRD-positive disease (the expected synthetic-lethality population), smaller but still significant in HRD-negative disease, and present in the overall all-comers population. This makes niraparib uniquely positioned for the broadest first-line ovarian maintenance population — including patients who do not have biomarker results in hand, and patients who are HRD-negative and would not qualify for the other PARPi 1L ovarian options.
The other FDA-approved PARP inhibitors for 1L ovarian maintenance — Lynparza (olaparib) SOLO-1 (BRCA-mutated 1L monotherapy maintenance) and PAOLA-1 (olaparib + bevacizumab in HRD-positive 1L maintenance) — require BRCA or HRD biomarker positivity for FDA-approved use. For BRCA-mutated or HRD-positive 1L ovarian, multiple PARPi options apply; for HRD-negative or biomarker-unknown 1L ovarian, Zejula is the only FDA-approved PARPi maintenance choice.
Four PARP inhibitors are FDA-approved. The class differs by indication breadth, biomarker requirements, dosing, and toxicity profile:
Curated subset of recruiting interventional Zejula (niraparib) trials in the ClinTrialFinder corpus as of June 27, 2026 (approximately 24 recruiting interventional trials total). Trials are grouped by clinical setting and ordered by phase and clinical significance.
Niraparib is being studied across multiple cancer types based on either documented BBB penetration (brain), BRCA / HRR mutation status (cross-cancer), or PARP-relevant biomarker biology (SLFN11). None of these cross-cancer indications are FDA-approved.
Showing a curated subset of recruiting Zejula (niraparib) interventional trials in the ClinTrialFinder corpus as of June 27, 2026 (approximately 24 recruiting interventional trials total). For the latest list: view all recruiting niraparib trials on ClinicalTrials.gov.
Target: PARP1 and PARP2 (poly ADP-ribose polymerase 1 and 2) — nuclear enzymes that sense single-strand DNA breaks, recruit DNA-repair machinery, and contribute to base excision repair and the broader DNA damage response. Niraparib is selective for PARP1/2 within the larger 17-member PARP family.
Mechanism step-by-step: (1) Niraparib enters the cell (oral, well-absorbed, BBB-penetrant) and binds the catalytic site of PARP1 and PARP2. (2) Catalytic inhibition blocks PARP-mediated single-strand break repair — unrepaired single-strand breaks accumulate. (3) During the next round of DNA replication, unrepaired single-strand breaks become double-strand breaks at replication forks. (4) Niraparib also "traps" PARP on chromatin — it stabilizes the PARP-DNA complex on damaged DNA, physically blocking replication-fork progression and amplifying double-strand-break generation. PARP trapping potency: talazoparib > niraparib > olaparib ≈ rucaparib. (5) In cells with intact homologous recombination (HR) repair (normal cells), the double-strand breaks are repaired with high fidelity — the cell survives. (6) In cells with defective HR (BRCA1/2-mutated, HRD-positive), the double-strand breaks cannot be repaired accurately; the cell accumulates damage and undergoes apoptosis. This is synthetic lethality — PARP inhibition is individually survivable; HR deficiency is individually survivable; combination is lethal.
Dosing: Oral, once daily, starting dose individualized: 200 mg for patients under 77 kg or with baseline platelet count under 150,000/microliter; 300 mg for patients at or above 77 kg and at or above 150,000/microliter platelet count. This weight-and-platelet-based starting dose was added to the label after the original approval to reduce thrombocytopenia-driven dose interruptions. Continue maintenance until disease progression or unacceptable toxicity. By contrast, Lynparza (olaparib) is dosed twice daily (300 mg BID); Talzenna (talazoparib) is dosed once daily at much lower milligrams (1 mg daily); Rubraca (rucaparib) is dosed twice daily.
BBB penetration: Niraparib has documented blood-brain-barrier penetration in preclinical models and Phase 1/2 glioma studies — a distinguishing pharmacology feature in the PARP class. This is the rationale behind the NCT06388733 Phase 3 in newly-diagnosed MGMT-unmethylated GBM (the first PARP Phase 3 in glioma) and the NCT06258018 niraparib + TMZ Phase 1/2 in glioma, and the NCT05700721 niraparib + dostarlimab in brain metastases. See the PARP Inhibitors mechanism hub for the cross-drug class comparison.
⚠ Distinctive Niraparib Toxicity: Thrombocytopenia (Low Platelets)
Thrombocytopenia (low platelet count) is the most patient-noticeable and most dose-limiting niraparib toxicity, and is substantially more pronounced with niraparib than with olaparib or rucaparib. Approximately 30% of patients experience Grade 3 or higher thrombocytopenia, and a meaningful fraction of patients drop their platelet count below 100,000/microliter — particularly in the first 1 to 3 months of treatment. Severe thrombocytopenia raises the risk of bleeding (typically minor — nosebleeds, easy bruising — but can be major in severe cases) and is the most common reason for dose interruption, dose reduction, or treatment discontinuation.
The FDA label was revised after the original approval to recommend a weight-and-platelet-based starting dose: 200 mg daily for patients under 77 kg or with baseline platelets under 150,000/microliter; 300 mg daily for patients at or above both thresholds. This individualized starting dose substantially reduces dose-interruption rates from thrombocytopenia. Routine CBC monitoring is intensive in the first few months (weekly for the first month, then biweekly, then monthly), with platelet-driven dose modifications built into the label. Patients should report any unusual bruising, nosebleeds, gum bleeding, or other bleeding signs promptly.
Anemia (low red blood cell count) is common with niraparib, frequently requires dose modification, and sometimes requires red-blood-cell transfusion. Fatigue from anemia is a major contributor to patient-reported quality of life on PARPi maintenance. Neutropenia (low white blood cell count) is less prominent with niraparib than with talazoparib but still common. Routine CBC monitoring catches both signals. Anemia and neutropenia, like thrombocytopenia, are most prominent in the first 1-3 months of dosing and tend to stabilize thereafter.
Hypertension (elevated blood pressure) is a niraparib-specific safety signal relative to other PARP inhibitors — both systolic and diastolic blood pressure elevations are reported, including some Grade 3 events. Blood pressure monitoring is part of routine niraparib care, particularly in the first 2 months. Patients with pre-existing hypertension may need anti-hypertensive medication adjustments. Tachycardia (elevated heart rate) is also reported. Patients with cardiovascular comorbidities should discuss the niraparib hypertension and tachycardia signals with their oncologist and cardiologist before starting treatment.
Secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are rare but documented late effects of PARP inhibitor treatment, observed in long-term follow-up across the PARPi class. The risk is highest in patients with extensive prior cytotoxic chemotherapy exposure (and the relevant comparator population — recurrent ovarian patients with multiple prior platinum / taxane regimens — has elevated baseline risk independent of PARPi). The absolute risk over the typical maintenance course appears low based on available data, but long-term surveillance continues to characterize this signal across all approved PARPi. The risk-benefit conversation is part of the informed-consent discussion before treatment.
What is Zejula (niraparib)?
Zejula is the brand name for niraparib (MK-4827), an oral, once-daily, selective PARP1/2 inhibitor developed originally by Merck (MK-4827), licensed to Tesaro Inc. (which obtained the original FDA approval), and acquired by GSK (GlaxoSmithKline) through the Tesaro acquisition in December 2018. Janssen holds prostate cancer rights to niraparib in certain territories. Niraparib selectively inhibits PARP1 and PARP2, two enzymes that participate in DNA single-strand break repair and the broader DNA damage response. By blocking PARP-mediated repair in tumors that already have homologous-recombination repair defects (BRCA1/2 mutations, HRD-positive tumors), niraparib exploits synthetic lethality — the cancer cell cannot repair accumulating DNA damage and undergoes apoptosis. Zejula is the FDA-approved PARP inhibitor with the broadest regulatory footprint within ovarian cancer: it is approved for first-line ovarian cancer maintenance regardless of BRCA or HRD status (PRIMA, April 2020), and for recurrent ovarian cancer maintenance after platinum response regardless of BRCA status (NOVA, March 2017). A third indication (October 2019) for HRD-positive heavily-pretreated recurrent ovarian (QUADRA) was voluntarily withdrawn in 2023. Niraparib's once-daily oral dosing (200 mg or 300 mg, individualized by baseline weight and platelet count) and documented blood-brain-barrier penetration distinguish it from other PARP inhibitors in the class.
Which patients qualify for Zejula?
Zejula is FDA-approved for adults with epithelial ovarian, fallopian tube, or primary peritoneal cancer in two maintenance settings. First indication (PRIMA, FDA-approved April 29, 2020): first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to first-line platinum-based chemotherapy — regardless of BRCA mutation or HRD status. This is the broadest indication of any FDA-approved PARP inhibitor: in real clinical practice, many patients do not yet have BRCA / HRD biomarker results at the moment maintenance decisions are made, and Zejula is the only PARP inhibitor approved for 1L maintenance without a biomarker requirement. PRIMA showed PFS benefit across all biomarker subgroups; the magnitude was largest in HRD-positive disease and smallest in HRD-negative disease, but benefit was statistically present in all subgroups. Second indication (NOVA, FDA-approved March 27, 2017): maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy — again regardless of BRCA mutation status. Zejula is given once daily orally, with the starting dose individualized to 200 mg or 300 mg based on baseline body weight (under 77 kg vs at or above 77 kg) and baseline platelet count (under 150,000/microliter vs at or above) — this weight-and-platelet-based starting dose was added to the FDA label after the original approval to reduce dose-interruption rates from thrombocytopenia. The previously-approved QUADRA indication (HRD-positive heavily-pretreated recurrent ovarian) was voluntarily withdrawn in 2023.
How is Zejula different from Lynparza (olaparib)?
Zejula (niraparib, GSK) and Lynparza (olaparib, AstraZeneca/Merck) are both FDA-approved oral PARP inhibitors and both exploit synthetic lethality in HR-deficient cancers, but their regulatory footprints, dosing, and biomarker positioning are meaningfully different. Lynparza was the first PARP inhibitor approved by the FDA (December 2014) and has the broadest cross-cancer footprint among PARPi: BRCA-mutated advanced ovarian (2014), BRCA-mutated HER2-negative metastatic breast (OlympiAD, January 2018), gBRCA metastatic pancreatic maintenance (POLO, December 2019), and BRCA / HRR-mutated mCRPC (PROfound, May 2020; PROpel + abiraterone 1L mCRPC, May 2023). Zejula's footprint is concentrated in ovarian cancer but has the broadest within-disease label: first-line ovarian maintenance regardless of BRCA or HRD status (PRIMA, April 2020) — the only PARPi approved for 1L ovarian maintenance without a biomarker requirement — and recurrent ovarian maintenance regardless of BRCA status (NOVA, March 2017). Practical sequencing for ovarian cancer: BRCA-mutated 1L (Lynparza SOLO-1 or Lynparza + bevacizumab PAOLA-1 are options; Zejula PRIMA also works); HRD-positive 1L without BRCA (PAOLA-1 olaparib + bev or PRIMA niraparib); HRD-negative or unknown biomarker 1L (Zejula PRIMA is the broadest-label option since other PARPi require BRCA / HRD); BRCA-mutated platinum-sensitive recurrent (SOLO-2 olaparib or NOVA niraparib both approved). Dosing: niraparib is once daily (200 mg or 300 mg, individualized) vs olaparib twice daily (300 mg BID). Toxicity profiles differ: niraparib has a more pronounced thrombocytopenia signal (prompting the weight-and-platelet-based starting-dose label revision) and hypertension; olaparib has a more pronounced anemia signal and a slightly higher nausea signal. See the Lynparza drug page for the BRCA / HRR cross-cancer discussion.
Is Zejula being tested in glioblastoma?
Yes — Zejula (niraparib) has the first PARP inhibitor Phase 3 trial in glioblastoma. NCT06388733 is a Phase 3 trial of niraparib vs temozolomide in newly-diagnosed MGMT-unmethylated glioblastoma — the population that derives little benefit from temozolomide because MGMT (the methylguanine methyltransferase repair enzyme) actively undoes the DNA damage that temozolomide is designed to cause. The trial rationale is that MGMT-unmethylated tumors have an intact DNA-damage repair pathway that minimizes TMZ benefit but creates a synthetic-lethality opportunity for PARP inhibition. Niraparib was selected for this Phase 3 specifically because it has documented blood-brain-barrier (BBB) penetration in preclinical models and Phase 1/2 glioma studies — a distinguishing pharmacology feature among PARP inhibitors. If the Phase 3 is positive, it would be a paradigm-shifting result on two levels: first, it would replace temozolomide (the Stupp protocol standard since 2005) for a major newly-diagnosed GBM subgroup; second, it would expand the PARP inhibitor class beyond its current ovarian / BRCA-mutated breast / mCRPC / pancreatic footprint into brain tumors. A companion Phase 1/2 trial (NCT06258018) tests niraparib + temozolomide in glioma — an alternative combination strategy. Other niraparib brain-related studies include NCT05700721 (niraparib + dostarlimab in brain metastases from solid tumors). See the Glioblastoma trials page for the full GBM trial landscape.
What are the main side effects of Zejula?
Zejula's distinctive side-effect profile is dominated by hematologic toxicity, with thrombocytopenia (low platelets) as the most patient-noticeable and dose-limiting effect — substantially more pronounced with niraparib than with olaparib or rucaparib. Approximately 30% of patients experience Grade 3 or higher thrombocytopenia, and a meaningful fraction of patients drop their platelet count below 100,000/microliter, particularly in the first 1-3 months of treatment. The FDA label was revised after the original approval to recommend a weight-and-platelet-based starting dose (200 mg for patients under 77 kg or with baseline platelets under 150,000; 300 mg for patients at or above both thresholds) to reduce dose-interruption rates. Routine CBC monitoring is intensive in the first few months, with platelet-driven dose modifications built into the label. Other common adverse events: anemia (also frequently requires dose modification or transfusion), neutropenia (less prominent than with talazoparib but still common), fatigue, nausea, vomiting, constipation, decreased appetite, headache, and insomnia. A distinctive niraparib safety signal relative to other PARP inhibitors is hypertension — systolic and diastolic blood pressure elevations are reported, including some Grade 3 events, and blood pressure monitoring is part of routine care during niraparib treatment. Tachycardia is also reported. Long-term: secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are rare but documented PARP class-wide late effects in long-term follow-up, particularly in patients with extensive prior cytotoxic chemotherapy exposure. The PARP class also carries a pneumonitis signal and a small fetal-toxicity signal (contraception required). See the PARP Inhibitors mechanism hub for the class-wide safety discussion.
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