Pharmaceutical firms’ war using PARP inhibitors, a group of pharmacological inhibitors of the enzyme poly ADP-ribose polymerase (PARP), is heating up in the ovarian cancer treatment market.
After AstraZeneca won approval for Lynparza (ingredient: olaparib) as the first PARP inhibitor to treat advanced ovarian cancer, Pfizer, Clovis Oncology, and GSK released rival drugs Talzenna (talazoparib), Rubraca (rucaparib), and Zejula (niraparib), respectively, in the U.S. and Europe.
Zejula is indicated as second-line maintenance therapy in ovarian cancer.
In a recent phase-3 PRIMA study, however, the drug proved efficacy as a first-line maintenance treatment in ovarian cancer patients regardless of BRCA mutation.
Zejula’s trial outcome became a challenge to AstraZeneca’s Lynparza. Zejula is the only PARP inhibitor that can be used not only for patients with BRCA mutations (15 percent) but also for non-BRCA patients (85 percent). If its indication gets expanded to the first-line maintenance therapy, it will threaten the status of Lynparza, observers said.
AstraZeneca on Wednesday announced the topline results of Lynparza’s new PAOLA-1 phase-3 study, signaling that the drug could be used as a first-line maintenance treatment regardless of patients’ BRCA mutation.
PAOLA-1 compared a combination therapy of Lynparza and Avastin (bevacizumab) to Avastin alone as a first-line maintenance treatment for patients with newly diagnosed ovarian cancer who responded to the first-line treatment with platinum-based chemotherapy and Avastin.
AstraZeneca said Lynparza and Avastin combo showed clinically meaningful improvement in progression-free survival (PFS) in the intent-to-treat (ITT) group.
“The positive results from the PAOLA-1 trial demonstrate a clear potential benefit of adding Lynparza to the standard-treatment bevacizumab for women with advanced ovarian cancer,” said José Baselga, executive vice president of Oncology R&D at AstraZeneca.
Following positive results from the SOLO-1 trial for women with a BRCA gene mutation, the PAOLA-1 test marks yet another positive phase-3 trial for Lynparza as a 1st-line maintenance treatment for women with advanced ovarian cancer, he added.
“We look forward to discussing the results with global health authorities as soon as possible.”
Although both PAOLA-1 study on Lynparza and PRIMA on Zejula aimed to check efficacy as a first-line maintenance treatment for ovarian cancer, the two have a significant difference.
While GSK compared Zejula with a placebo, AstraZeneca compared Avastin and Lynparza combo with Avastin alone.
AstraZeneca’s Vice President of Oncology Greg Rossi said Avastin was the standard therapy in many markets including Europe and that combining it with a PARP inhibitor could create a synergy effect in non-BRCA patients.
However, GSK’s Chief Scientific Officer Hal Barron countered Rossi’s claim in the second-quarter earnings report.
Barron raised the issue of toxicity and additional cost of Lynparza and Avastin combo and said Avastin was not a standard therapy in the U.S. Only 25 percent of ovarian cancer patients used Avastin as the first-line maintenance therapy, he noted.
Takeda Pharmaceutical has the sales right for Zejula in Korea, Japan, Taiwan, Russia, and Australia. In other markets, GSK owns the sales license.
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