GlaxoSmithKline’s PARP inhibitor Zejula has been approved for wider use in some cancers.
Zejula got a green signal for wider use. (nitpicker/Shutterstock)
GlaxoSmithKline’s PARP inhibitor Zejula has been approved for wider use in some cancers. The latest approval from the U.S. Food and Drug Administration (FDA) sees Zejula widening the use of PARP inhibitors beyond the narrow scope initially thought.
The U.S. Food and Drug Administration expanded Zejula’s ( niraparib) approved treatments to include previously treated patients with advanced ovarian, fallopian tube, or primary peritoneal cancer patients. The new indication is for those 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.
GSK said this approval represented 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, GSK exclaimed.
“This new indication reinforces our commitment to providing treatment options for more women impacted by ovarian cancer, especially those with high unmet needs. We look forward to continuing our clinical development program of Zejula and understanding its full potential as a treatment for people living with ovarian cancer,” Ales Hoos, head of oncology R&D at GSK said in a statement.
The approval is significant as it reinforces the belief that PARP inhibitors can play a much larger role in treating cancer than just those tied to a BRCA mutation. A recent study conducted by UT Southwestern has shown that PARP inhibitors could have broader effectiveness in treating other types of cancer, including ovarian and prostate cancer. PARP stands for poly ADP ribose polymerase, which is an enzyme many cancer cells are more dependent upon than regular, healthy cells are. PARP inhibitors are designed to disable DNA repair pathways in cancer cells, which make it difficult for those cells to survive.
The latest approval for Zejula, which GSK gained from its $5.1 billion acquisition of Tesaro Oncology last year, was based on the mid-stage QUADRA study. The single-arm study represented a real-world, difficult-to-treat patient population with high unmet needs, the company noted. The QUADRA study was also 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. In the QUADRA trial, Zejula demonstrated a clinically meaningful and durable benefit in the treated patients, with an objective response rate (ORR) of 24%. A median duration of response (mDOR) of 8.3 months was observed, the company reported.
Zejula was initially approved by the FDA in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Ovarian cancer impacts nearly a quarter-of-a-million women in the United States. It is estimated that about 85% with an advanced form of the diseases will see it return.
The new approval for Zejula comes at a good time for GSK as Zejula competes for market share with other PARP inhibitors, such as AstraZeneca’s and Merck’s Lynparza. Last year, GSK laid out a new R&D strategy that focuses on the development of medicines that target mechanisms of action with strong human genetic validations.
In August, AstraZeneca reported that for the second time, Lynparza met its endpoints as a potential first-line treatment for ovarian cancer in a Phase III trial. The Phase III PAOLA-1 trial assessed Lynparza as a companion to the standard of care treatment Bevacizumab (Genentech’s Avastin) in women with advanced ovarian cancer.
