Niraparib (ZEJULA)

On March 27, 2017 , the U.S. Food and Drug Administration approved niraparib (ZEJULA, Tesaro, Inc.), a poly ADP-ribose polymerase (PARP) inhibitor, for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

Approval was based on a randomized trial (NOVA) of 553 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received at least two prior treatments of platinum-based chemotherapy and were in a complete or partial response to the most recent chemotherapy treatment. Patients were randomized (2:1) within 8 weeks of the last therapy to either niraparib (300 mg orally daily) or matched placebo. Patients were assigned to one of two cohorts based on the BRACAnalysis CDx. Patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm) were assigned to the germline BRCA- mutated (gBRCAmut) cohort (n=203), and those without germline BRCA mutations were assigned to the non-gBRCAmut cohort (n=350).

The trial demonstrated a statistically significant improvement in progression-free survival (PFS) for patients randomized to niraparib compared with placebo in both cohorts. The estimated median PFS for those taking niraparib who had a germline BRCA mutation was 21 months compared with 5.5 months for those in the gBRCAmut cohort receiving placebo (HR=0.26; 95% CI: 0.17, 0.41; p<0.0001). The estimated median PFS for those taking niraparib who did not have a germline BRCA mutation was 9.3 months compared with 3.9 months for those patients in the non-gBRCAmut cohort receiving placebo (HR=0.45; 95% CI: 0.34, 0.61; p<0.0001).

Niraparib’s safety was evaluated in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in the NOVA trial. The most common adverse reactions occurring in at least 10% of patients receiving niraparib were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension. Myelodysplastic syndrome and/or acute myeloid leukemia occurred in 5 of 367 (1.4%) patients receiving niraparib and in 2 of 179 (1.1%) patients assigned to placebo. Grade 3-4 hypertension occurred in 9% of niraparib- treated patients compared with 2% of patients assigned to placebo.

The recommended dose and schedule of niraparib is 300 mg taken once daily with or without food.

Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designation, as well as Orphan Drug designation specifically for treating recurrent epithelial ovarian cancer. FDA approved this application approximately three months ahead of the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online athttp://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).