Zai Lab announced its partner GlaxoSmithKline (GSK) has received approval from the U.S. Food and Drug Administration (FDA) for an expanded indication for Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer patients, who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy. Patient selection is based on an FDA-approved companion diagnostic for Zejula.
This represents the first time a PARP inhibitor has been approved for use in patients beyond those with a BRCA-positive (BRCA+) mutation as monotherapy in the late-line treatment setting. Now women with late-line, HRD-positive (HRD+) disease are eligible to be treated with a PARP inhibitor.
This new indication in the U.S. is based on the QUADRA study, a Phase 2, multi-center, open-label, single-arm clinical study representing a real world, difficult-to-treat patient population with high unmet needs. QUADRA is the largest clinical trial of a PARP inhibitor in women who received three or more treatments for advanced ovarian cancer. The trial enrolled a broad patient population including women with BRCA+ platinum-sensitive, resistant and refractory disease as well as women with HRD+ platinum-sensitive disease.
Clinically meaningful and durable benefit was demonstrated in the FDA-indicated patient population with an objective response rate (ORR) of 24% (95% CI, 16–34). A median duration of response (mDOR) of 8.3 months (95% CI, 6.5–not estimable) was observed.
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Additional analyses were conducted in various sub populations where efficacy of Zejula was also demonstrated for patients with tBRCA and GIS; defined as deleterious or suspected deleterious somatic or germline BRCA mutation and genomic instability score (GIS ≥42) as identified with FDA approved companion diagnostic test, respectively:
- tBRCA+ platinum-sensitive disease, ORR of 39% (95% CI, 17,64);
- tBRCA+ platinum-resistant disease, ORR of 29% (95% CI, 11,52);
- tBRCA+ platinum-refractory disease, ORR of 19% (95% CI, 4,46); or
- non-BRCA mut, GIS-positive, platinum-sensitive disease, ORR of 20% (95% CI, 8,37).
The safety profile was consistent with that seen in the Phase 3 NOVA trial in the recurrent maintenance population. Most common grade ≥3 adverse reactions reported in ≥10% of patients in the QUADRA study included thrombocytopenia (28%), anemia (27%), neutropenia (13%) and nausea (10%).
Zai Lab plans to leverage the QUADRA study to accelerate the approval pathway in China for this additional indication.
Niraparib is a highly potent and selective oral, once-daily small molecule poly (ADP-ribose) PARP 1/2 inhibitor. It was approved in March 2017 by the FDA in the United States and in November 2017 by the EMA in the European Union under the trade name Zejula as a maintenance treatment for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Based on the approval status in the United States and European Union by our partner, GSK, Zai Lab obtained the approval for marketing Zejula in Hong Kong in October 2018 and Macau in June 2019.