Lynparza Bags Multiple Approvals in Japan

On December 28th, Merck and AstraZeneca announced that their PARP inhibitor Lynparza received approval from Japan to treat ovarian, prostate, and pancreatic cancers. The approvals by the Japanese Ministry of Health, Labor, and Welfare are based on Phase 3 clinical trials PAOLA-1, PROfound, and POLO, the results of which have been published in The New England Journal of Medicine.

Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, commented, “For patients in Japan diagnosed with each of these types of cancer, there are very few treatment options. Approvals for treatments such as Lynparza, the first PARP inhibitor to be approved in these specific types of metastatic castration-resistant prostate cancer and metastatic pancreatic cancer in Japan, enable us to advance this evolving era of personalized medicine and change how these cancers are treated.”

The three approvals bagged by Lynparza is to be used as a maintenance treatment after first-line chemotherapy consisting of bevacizumab in patients with homologous recombination repair deficient (HRD) ovarian cancer; patients with BRCA gene-mutated (BRCAm) castration-resistant prostate cancer with distant metastasis (mCRPC), and finally after platinum-based chemotherapy in patients with BRCAm curatively unresectable pancreatic cancer.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, further added, “These three approvals allow patients in Japan to be treated with Lynparza, a targeted treatment personalized to their specific biomarkers. They further underline the critical importance of biomarker testing at diagnosis, which helps physicians determine a course of treatment tailored to their individual patients to substantially delay disease progression.”

PAOLA-1 Clinical Trial

Ovarian cancer ranks fifth in cancer-related deaths amongst women. The American Cancer Society estimates that in the year 2020 alone, approximately 21,750 women will be diagnosed with ovarian cancer, with 13,940 deaths. PAOLA-1, a double-blinded, Phase 3 trial, showed that Lynparza in combination with bevacizumab maintenance treatment helped in alleviating the risk of disease progression or death by almost 67% in patients with HRD-positive advanced ovarian cancer. The addition of Lynparza improved progression-free survival to a median of 37.2 months as compared to 17.7 months with bevacizumab alone. The major adverse effects were nausea and fatigue.

PROfound Clinical Trial

PROfound, a Phase 3 clinical trial investigated the safety and efficacy of Lynpraza in patients with HRR-mutated genes, BRCA1/2, and ATM. Lynparza met its primary endpoint, reduced the risk of death by 78%, and improved progression-free survival to 9.8 months compared to 3 months in patients treated with placebo. Further, Lynparza treatment improved overall survival from 14.4 months to 20.1 months in patients with HRR mutations.

POLO Clinical Trial

POLO is a Phase 3 double-blinded clinical trial that investigated the potential of Lynparza as maintenance monotherapy in mBRCA metastatic cancer patients. A total of 154 patients were randomly assigned to receive Lynparza or placebo, and the primary endpoint of the study was overall survival. Lynparza nearly doubled progression-free survival from 3.8 months in placebo patients to 7.4 months.

Competitors

In the field of BRCA-mutated ovarian cancer, Lynparza faces stiff competition from GlaxoSmithKline’s Zejula alongside Clovis Oncology’s Rubraca, which is threatening its market share. However, Zejula might prove to be the thorn on Lynparza’s way with its newly armed FDA approval for use in women who haven’t yet relapsed.

In patients with BRCA1, BRCA2, or ATM mutations specifically, Lynparza has shown that it can reduce the risk of disease progression by approximately 66%, which is considerably higher than fellow competitors such as Johnson & Johnson’s Zytiga or Pfizer and Astellas’ Xtandi. All this data looks extremely promising for Lynparza as it prepares to take the Japanese pharmaceutical market by storm.

Related Article: Lynparza Greenlighted by FDA for HRR-Mutated, Metastatic Prostate Cancer

References

1. https://www.businesswire.com/news/home/20201228005064/en/LYNPARZA

Author

Tulip Chakraborty