FDA Approves Niraparib for HRD-Positive Advanced Ovarian Cancer Patients

Today, the U.S. FDA announced the approval of an expanded indication for GlaxoSmithKline’s (GSK) niraparib (brand name Zejula) for the treatment of patients with advanced ovarian cancer who have received more than three prior lines of chemotherapy. These patients must have homologous recombination deficiency (HRD)-positive tumors. HRD is defined as the presence of BRCA gene mutations or genomic instability observed in patients whose disease progressed more than six months after responding to platinum-based chemotherapy.

Niraparib is a key PARP inhibitor acquired by GSK following its $5.1 billion purchase of TESARO last year. PARP inhibitors are anticancer drugs developed based on the principle of “synthetic lethality.” By inhibiting the PARP-mediated DNA damage repair mechanism, they cause an accumulation of excessive DNA damage in tumors harboring BRCA gene mutations, thereby inducing cell death. Initially, PARP inhibitors were believed to be effective only in patients with BRCA gene mutations. However, clinical trials conducted by TESARO demonstrated that PARP inhibitors can also exert therapeutic effects in tumors with homologous recombination deficiency.

This approval was based on the results of QUADRA, an open-label, single-arm Phase 2 clinical trial. In this trial, researchers found that Zejula demonstrated efficacy not only in patients with BRCA gene mutations (with an overall response rate of 29%), but also in patients without BRCA gene mutations who had homologous recombination deficiency (with an overall response rate of 15%). In patients without BRCA gene mutations and without homologous recombination deficiency, Zejula achieved an overall response rate of 3%. The results of this trial have been published in The Lancet Oncology.

▲Performance of Zejula in patients with different types of ovarian cancer in the QUADRA trial (Image source: Reference [2])

Expanding the indications for Zejula in ovarian cancer is one of GSK’s key R&D priorities. At the recent ESMO Congress, Dr. Hal Barron, Chief Scientific Officer and President of R&D at GSK, stated that Zejula possesses unique pharmacokinetic properties. It may not only exert efficacy in patients with homologous recombination deficiency (HRD) through the mechanism of synthetic lethality, but also demonstrate activity in tumors without HRD via alternative pathways. Data from the PRIMA trial presented at the ESMO Congress further indicated that Zejula, as a first-line maintenance therapy, is effective across all patients with ovarian cancer.

Image source: Reference [3]

We look forward to Zejula benefiting more patients with ovarian cancer.

References:

[1] FDA approves niraparib for HRD-positive advanced ovarian cancer. Retrieved October 23, 2019, from https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-hrd-positive-advanced-ovarian-cancer

[2] Moore et al., (2019). Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncology, https://doi.org/10.1016/S1470-2045(19)30029-4

[3] ESMO Investor call: accelerating our oncology Pipeline. Retrieved October 23, 2019, from https://www.gsk.com/media/5717/esmo-presentation-30-september.pdf

▽Follow [WuXi AppTecDe】WeChat Official Account