European Commission approves Zejula (niraparib) as first-line monotherapy maintenance treatment in advanced ovarian cancer

For media and investors only

Issued: London, UK

• Zejula is the first PARP inhibitor approved as monotherapy in the European Union for patients with platinum-responsive advanced ovarian cancer, regardless of biomarker status

GlaxoSmithKline (GSK) plc today announced the European Commission has approved Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as first-line monotherapy maintenance treatment for adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following platinum-based chemotherapy. This approval makes Zejula the only PARP inhibitor approved in the European Union for use as a monotherapy for patients with advanced ovarian cancer, regardless of their biomarker status.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “Over 65,000 women in Europe are diagnosed with ovarian cancer each year.^[i] This approval of Zejula means that many more women will have the option to receive this innovative medicine earlier, potentially extending the time they may spend without their devastating cancer progressing.”

In April 2020, the US Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for Zejula in the United States for the same indication, which is supported by data from the pivotal phase 3 PRIMA study (ENGOT-OV26/GOG-3012) that demonstrated a clinically meaningful progression-free survival benefit of Zejula in the first-line maintenance setting. The PRIMA study enrolled patients with newly diagnosed advanced ovarian cancer who responded to first-line treatment with platinum-based chemotherapy, a population with high unmet needs and limited treatment options.

Dr Antonio Gonzalez-Martin, Co-Director, Department of Medical Oncology, Clinica Universidad de Navarra, Spain, and Primary Investigator for PRIMA, said: “Until now, only women with BRCA-mutant (BRCAm) ovarian cancer, representing just 20% of patients with advanced ovarian cancer, were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting.[ii] Expanding the potential use of Zejula, regardless of biomarker status, is an important step forward in treating this challenging cancer.”

The primary endpoint in the PRIMA study was progression free survival analysed sequentially, first in the homologous recombination deficient (HRd) population, then in the overall population. The PRIMA study significantly improved PFS for patients treated with Zejula, regardless of biomarker status. In the HRd population, Zejula resulted in a 57% reduction in the risk of disease progression or death vs. placebo (HR 0.43; 95% CI, 0.31 to 0.59; p<0.0001) and a 38% reduction in the risk of disease progression or death vs. placebo in the overall population (HR 0.62; 95% CI, 0.50 to 0.76; p<0.001). In addition, there was a 60% reduction in risk of progression in those with BRCA mutation tumours (HR 0.40; 95% CI, 0.27 to 0.62; p<0.001).

Zejula’s safety profile, as demonstrated by the PRIMA results, was consistent with the previously observed clinical safety profile. At initiation of the PRIMA study, patients received a fixed starting dose of 300 mg of Zejula once-daily. The study was later amended to incorporate an individualised starting dose of either 200 mg or 300 mg of Zejula once-daily based on the patient’s baseline weight and/or platelet count. Lower rates of grade 3 and 4 haematologic treatment-emergent adverse events were observed with an individualised starting dose, compared to the overall population, including thrombocytopenia (21% compared to 39%), anaemia (23% compared to 31%) and neutropenia (15% compared to 21%).  

Based on these results, the Zejula EU prescribing information has been updated to include the individualised starting dose once-daily based on the patient’s baseline weight and/or platelet count.

Clara MacKay, Chief Executive Officer, World Ovarian Cancer Coalition, said: “Having a new first-line maintenance option for patients with platinum-responsive advanced ovarian cancer in Europe — regardless of BRCA mutation status — speaks to the important role of PARP inhibitors in the fight against ovarian cancer. We are especially delighted that today's approval means that more women in Europe who are diagnosed with ovarian cancer will have this new treatment option. We appreciate the commitment and scientific leadership required to develop innovative new therapies that address unmet needs in women’s cancer.”

About Ovarian Cancer

In Europe, ovarian cancer is the sixth deadliest cancer among women[iii] and more than 65,000 women are diagnosed each year.ⁱ Despite high response rates to platinum-based chemotherapy in the first-line, approximately 85% of women with advanced ovarian cancer will see their disease return.[iv] With each recurrence, the time a woman may spend without her cancer progressing gets shorter.

About Zejula (niraparib)

Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies.

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cell therapy, either alone or in combination.

Important Information for ZEJULA

Zejula approved indication:

Zejula is indicated as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

Important Safety Information

Contraindications: Hypersensitivity to niraparib or to any of the excipients and breast-feeding.

Warnings and precautions: Test complete blood counts (CBC) weekly for the first month of treatment, followed by monthly monitoring for the next 10 months of treatment and periodically after this time. This is recommended to monitor for clinically significant changes in any haematologic parameter during treatment. If a patient develops severe persistent haematologic toxicity (thrombocytopenia, anaemia and neutropenia including pancytopenia) that does not resolve within 28 days following interruption, Zejula should be discontinued. Patients with lower body weight or lower baseline platelet count may be at increased risk of Grade 3+ thrombocytopenia. Due to the risk of thrombocytopenia, anticoagulants and medicinal products known to reduce the thrombocyte count should be used with caution. If MDS and/or AML are confirmed while being prescribed Zejula, treatment should be discontinued, and the patient treated appropriately. Hypertension, including hypertensive crisis, has been reported with the use of Zejula. Pre‑existing hypertension should be adequately controlled before starting Zejula treatment. Zejula should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy. There have been reports of Posterior Reversible Encephalopathy Syndrome (PRES) in patients receiving Zejula. In case of PRES, it is recommended to discontinue treatment. Patients with galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine. Tartrazine may cause allergic reactions. Paediatric safety and efficacy has not yet been established.

Undesirable effects: The most common serious adverse reactions were thrombocytopenia and anaemia.            

Very common (≥1/10): anaemia, thrombocytopenia, nausea, fatigue, constipation, vomiting, headache, insomnia, platelet count decreased, neutropenia, abdominal pain, decreased appetite, diarrhoea, dyspnoea, hypertension, asthenia, dizziness, neutrophil count decreased, cough, arthralgia, back pain, white blood cell count decreased, and hot flush.

Common (≥1/1000 to <1/10): bronchitis, conjunctivitis, leukopenia, hypersensitivity, hypokalemia, anxiety, depression, dysgeusia, tachycardia, hypertension, epistaxis, dry mouth, abdominal distension, mucosal inflammation (including mucositis), stomatitis, photosensitivity, rash, myalgia, oedema peripheral, fatigue, asthenia, Gamma-glutamyl transferase increased, AST increased, blood creatinine increased, ALT increased, blood alkaline phosphatase increased and weight decreased.

Refer to the Zejula Prescribing Information for a full list of adverse events and the complete important safety information.

About GSK  

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us. 

[i] The World Ovarian Cancer Coalition Atlas: Global Trends in Incidence, Mortality and Survival. World Ovarian Cancer Coalition; 2018. https://worldovariancancercoalition.org/wp-content/uploads/2018/10/THE-WORLD-OVARIAN-CANCER-COALITION-ATLAS-2018.pdf. Accessed October 19, 2020.

[ii] Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D'Andrea AD. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015;5(11):1137-54.

[iii] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-E386. doi:10.1002/ijc.29210.

[iv] Lorusso D, Mancini M, Di Rocco R, Fontanelli R, Raspagliesi F. The role of secondary surgery in recurrent ovarian cancer [published online August 5, 2012]. Int J Surg Oncol. 2012. doiL10.1155/2012/613980.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D "Risk Factors" in the company's Annual Report on Form 20-F for 2019 and as set out in GSK’s “Principal risks and uncertainties” section of the Q3 Results and any impacts of the COVID-19 pandemic.