European Medicines Agency accepts submission of GSK's Marketing Authorisation Application for Zejula (niraparib) in first-line maintenance treatment for women with platinum-responsive advanced ovarian cancer

-  Submission based on data from the Phase III PRIMA clinical study that demonstrated clinically meaningful outcomes of niraparib maintenance treatment in the first-line setting regardless of biomarker status

LONDON, Feb. 27, 2020 /PRNewswire/ -- GlaxoSmithKline plc announced that the European Medicines Agency (EMA) has validated the company's Type II Variation (T2V) for Zejula (niraparib) as a maintenance treatment in the first-line setting for women with advanced ovarian cancer who responded to platinum-based chemotherapy regardless of biomarker status. Validation of the T2V confirms that the submission is accepted and begins the formal review process by the EMA's Committee for Human Medicinal Products (CHMP).

The submission is based on data from the PRIMA study (ENGOT-OV26/GOG-3012), which demonstrated clinically meaningful outcomes of niraparib treatment in the first-line maintenance setting.ⁱ Results from the PRIMA study were presented at the 2019 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine. The PRIMA study enrolled women who responded to first-line treatment with platinum-based chemotherapy, including those with high risk of disease progression, a population with high unmet need and previously under-represented in first-line ovarian cancer studies.

In Europe, ovarian cancer is the sixth deadliest cancer among women and more than 65,000 women are diagnosed each year.ⁱⁱ Most women are diagnosed with advanced (stage III or IV) ovarian cancer and have a five-year survival rate of ~30%.ⁱⁱⁱ 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 until the next recurrence gets shorter.

About PRIMA
PRIMA is a double-blind, randomised Phase III study designed to evaluate niraparib versus placebo in women being treated first-line for stage III or IV ovarian cancer. The study assessed the efficacy of niraparib as maintenance therapy, as measured by progression free survival. Patients in complete or partial response to first-line platinum-based chemotherapy were randomised 2:1 to niraparib or placebo.

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, including a Phase III study as a first-line triplet maintenance treatment in ovarian cancer (FIRST).

Important Information for ZEJULA

Zejula approved indication:
Zejula is indicated as 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 response (complete or partial) to 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 weekly for the first month of treatment, then monthly thereafter. If a patient develops severe persistent haematologic toxicity including pancytopenia that does not resolve within 28 days following interruption, Zejula should be discontinued. 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. 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): urinary tract infection, thrombocytopenia, anaemia, neutropenia, decreased appetite, insomnia, headache, dizziness, dysgeusia, palpitations, hypertension, dyspnea, cough, nasopharyngitis, nausea, constipation, vomiting, abdominal pain, diarrhoea, dyspepsia, back pain, arthralgia, fatigue, asthenia.

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

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

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 cells, either alone or in combination.

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.

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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.

Registered in England & Wales:
No. 3888792

Registered Office:
980 Great West Road
Brentford, Middlesex
TW8 9GS

ⁱ González-Martín A, Pothuri B, Vergote I, Christensen R, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine. 2019. doi: 10.1056/NEJMoa1910962
ⁱⁱ World Health Organization. Globocan 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. Accessed January 16, 2020.
ⁱⁱⁱ 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 January 14, 2020.
^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.

SOURCE GlaxoSmithKline plc