On December 15, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that ZEJULA (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, is now available by prescription in Germany (Press release, TESARO, DEC 15, 2017, View Source [SID1234522658]). ZEJULA is also currently available for patients in the United Kingdom (UK) who have private insurance. On November 16, the European Commission (EC) approved ZEJULA as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response (CR) or partial response (PR) to platinum-based chemotherapy. ZEJULA is the first once-daily, oral PARP inhibitor to be approved in Europe that does not require BRCA mutation or biomarker testing.

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"As we continue to globalize our mission, we remain committed to enabling access to this important therapy for patients who have completed platinum-based chemotherapy and have limited treatment options. In the U.S., where ZEJULA has been approved since March, it is the most frequently prescribed PARP inhibitor for patients with ovarian cancer," said Orlando Oliveira, Senior Vice President and General Manager of TESARO International. "The introductions of ZEJULA in Germany and the UK are significant milestones for TESARO as we bring transformative therapies to patients with cancer around the globe. With two approved products in Europe, we are working quickly to make our medicines available in the 17 European countries where we have a direct presence."

The EC approval of ZEJULA was based on data from the clinically rigorous ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. The primary endpoint of the trial was progression free survival (PFS). Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by a robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with or without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (hazard ratio (HR) 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

In the ENGOT-OV16/NOVA trial, the most common grade 3/4 adverse reactions to ZEJULA included thrombocytopenia (34%), anemia (25%), neutropenia (20%), and hypertension (8%). Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low, approximately 1% after month three. The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3%, 2% and 1% of patients, respectively.

The approved starting dose of ZEJULA is 300 milligrams once per day. According to the European summary of product characteristics (SmPC), in patients below 58 kilograms, a starting dose of 200 milligrams once per day may be considered. The most commonly administered dose of ZEJULA over the course of the Phase 3 NOVA clinical trial was 200 milligrams once per day, following dose modification. Further exploratory analyses of the NOVA study indicated that individual dose modification maintained efficacy and reduced the rate of new adverse events1.

About Ovarian Cancer in Europe
Europe has one of the highest incidences of ovarian cancer in the world with approximately 45,000 women diagnosed each year2,3. In the European Union, ovarian cancer is the sixth-most common cancer and the fifth-most frequent cause of cancer death among women there2,4. Despite high initial response rates to platinum-based chemotherapy, approximately 85% of women with advanced ovarian cancer will experience a recurrence of the disease after first-line treatment5. The efficacy of chemotherapy also diminishes over time.

About ZEJULA (niraparib)
ZEJULA is a once-daily, oral poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the European Union as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in 1.4% of patients receiving ZEJULA vs. 1.1% of patients receiving placebo in the Phase 3 NOVA trial, and 0.9% of patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Monitor complete blood counts (CBCs) weekly for the first month of treatment and modify the dose as needed. After the first month, it is recommended to monitor CBCs for the next 10 months of treatment, and periodically after this time. Based on individual laboratory values, weekly monitoring for the second month may be warranted.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Pre-existing hypertension should be adequately controlled before starting ZEJULA. Monitor blood pressure monthly for the first year and periodically thereafter during treatment with ZEJULA. ZEJULA should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the possible risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain, diarrhea, dyspepsia, urinary tract infection, fatigue/asthenia, decreased appetite, headache, dizziness, dysgeusia, palpitations, insomnia, nasopharyngitis, dyspnea, cough, and hypertension.