AstraZeneca, Merck's Lynparza snags first-in-class FDA nod for early breast cancer

Lynparza is solidifying its lead as the top-selling PARP inhibitor with a first-of-its-kind FDA approval.

The FDA greenlighted the AstraZeneca and Merck drug for a specific group of patients with high-risk early breast cancer after chemotherapy treatment either before or after surgery, the two companies said Friday. The patient’s tumor must bear germline BRCA mutations and be HER2-negative.

About 91% of all breast cancer patients in the U.S. are diagnosed at an early stage, with BRCA mutations found in about 5% to 10% of cases, according to the pharma partners. The FDA go-ahead makes Lynparza the first PARP inhibitor—and the first targeted therapy—for the post-surgery breast cancer setting known as adjuvant treatment.

Based on the patient population, SVB Leerink analyst Andrew Berens, M.D., figured the ajudvant breast cancer setting could be a $1.5 billion opporunity for Lynparza.

For this approval, Lynparza proved its mettle in the phase 3 OlympiA trial. Compared with placebo, the targeted drug significantly reduced the risk of invasive breast cancer recurrences, disease progression or death by 42%. Last year, when investigators presented those invasive disease-free survival data during the plenary session at the American Society of Clinical Oncology meeting, Lynparza had already shown a promising sign that it could help patients live longer.

Now, an updated analysis has confirmed a “statistically significant and clinically meaningful” improvement in patient survival. Lynparza pared down the risk of death by 32% over placebo, AZ and Merck said.

It can be difficult for cancer drugs in early treatment settings to show a large survival benefit given that multiple subsequent therapies could blur the effect. The overall survival showing arms Lynparza with one powerful piece of clinical evidence to convince doctors, even though driving BRCA testing might be a challenge.

Before the new nod, Lynparza was approved in the U.S. to treat BRCA-mutated metastatic breast cancer previously treated with chemotherapy.

The PARP inhibitor is the best selling drug in its class, boasting multiple indications in cancer types including prostate cancer, ovarian cancer and pancreatic cancer. Last year, Lynparza reeled in $2.35 billion sales for AZ, a 30% increase from 2020 at constant exchange rates.

Other marketed PARP inhibitors, namely GlaxoSmithKline’s Zejula, Clovis Oncology’s Rubraca and Pfizer’s Talzenna, don’t have any company-sponsored phase 3 trials in adjuvant breast cancer.

Meanwhile, AZ and Merck recently touted another important win for Lynparza in newly diagnosed metastatic, castration-resistant prostate cancer, showing that its addition to Johnson & Jonson’s Zytiga and a steroid extended the time patients could live without disease progression regardless of their homologous recombination repair (HRR) genetic mutation status. BRCA genes are part of the HRR gene panel.

In addition, Merck is evaluating Lynparza with or without Roche’s Avastin in colorectal cancer as a first-line maintenance therapy in patients who have not progressed on an induction treatment. Data from that phase 3 LYNK-003 trial are expected next year.