AstraZeneca and Merck, known as MSD outside the United States and Canada, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending a marketing authorization of Lynparza (olaparib) tablets (300 mg twice daily) for use as a maintenance therapy for patients with platinum-sensitive relapsed high grade, epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response or partial response to platinum-based chemotherapy. Lynparza is recommended for treatment in this setting regardless of patients’ BRCA mutation status.
Sean Bohen, executive vice president, global medicines development and chief medical officer at AstraZeneca, said, “The data show that Lynparza provides long-term disease control, delaying the need for further chemotherapy for this broader group of women with platinum-sensitive relapsed ovarian cancer, irrespective of their BRCA status. It also offers a well-characterized safety and tolerability profile, which is critical to help enable patients to stay on treatment.”
Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, “We welcome this positive opinion based upon data which indicate the potential impact for Lynparza as maintenance therapy for women with platinum-sensitive relapsed ovarian cancer. We look forward to our continued work with AstraZeneca to bring Lynparza to patients in the EU.”
The CHMP recommendation is based on two randomized trials, SOLO-2 and Study 19, which showed Lynparza (olaparib) reduced the risk of disease progression or death for platinum-sensitive relapsed patients compared to placebo.
The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy (=10%) were nausea, vomiting, diarrhoea, dyspepsia, fatigue, headache, dysgeusia, decreased appetite, dizziness and anaemia.
Lynparza, the first poly ADP-ribose polymerase (PARP) inhibitor approved, was initially licensed as a capsule formulation. The new tablet formulation will reduce dosing from eight capsules twice daily to two tablets twice daily.
Lynparza is available in nearly 60 countries and has treated more than 20,000 patients globally. It has the broadest clinical development program of any PARP inhibitor, and AstraZeneca and Merck are working together to bring Lynparza to more patients across multiple cancers. In January 2018, Lynparza was approved by the US Food and Drug Administration for use in metastatic breast cancer, becoming the first PARP inhibitor licensed beyond ovarian cancer.
SOLO-2 was a phase 3, randomized, double-blinded, multicenter trial designed to determine the efficacy of Lynparza (olaparib) tablets compared to placebo as maintenance monotherapy in patients with platinum-sensitive relapsed or recurrent germline BRCA-mutated ovarian, fallopian tube and primary peritoneal cancer. The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomized 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least two prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomized to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.
Study 19 was a phase 2, randomized, double-blinded, placebo-controlled, multicenter trial, which evaluated the efficacy and safety of Lynparza compared with placebo in relapsed, high-grade serous ovarian cancer patients. The trial randomized 265 patients regardless of BRCA mutation status and who had completed at least two courses of platinum-based chemotherapy and their most recent treatment regimen. Eligible patients were randomized to receive Lynparza maintenance monotherapy at a dose of 400mg per day or matching placebo.
Lynparza is a first in-class poly ADP-ribose polymerase (PARP) inhibitor and the first targeted treatment to potentially exploit tumour DNA damage response (DDR)-pathway deficiencies to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.
In July 2017, AstraZeneca and Merck (known as MSD outside the United States and Canada) announced a global strategic oncology collaboration to co-develop and co-commercialize Lynparza (olaparib), the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumour types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.