AstraZeneca’s Lynparza (ingredient: olaparib) and Takeda’s Zejula (niraparib) work in the same mechanism to target progressive ovarian cancer with poor survival and frequent recurrence.
However, the two companies have taken a different approach to promote their drugs, drawing attention in the pharmaceutical industry.
On Friday, the U.S. Food and Drug Administration approved the combination of two drugs, Lynparza and Avastin (bevacizumab), as the first-line maintenance therapy for patients with advanced ovarian cancer who have experienced a complete or partial response to the previous platinum-based chemotherapy, and have cancer that expresses homologous recombination deficiencies (HRD).
The nod was based on results of the phase-3 PAOLA-1 study that the combo of Lynparza and bevacizumab reduced the risk of disease progression and death by 67 percent, compared to the bevacizumab monotherapy.
As the first poly ADP ribose polymerase (PARP) inhibitor, Lynparza obtained approval as the monotherapy for the first-line maintenance therapy in patients with a BRCA gene mutation. However, only 15-20 percent are BRCA mutation-positive in ovarian cancer patients. Thus, the latest green light widened the population for Lynparza from 15 percent to over 50 percent of progressive ovarian cancer patients.
The latecomer Zejula won approval in April as first-line maintenance treatment for advanced ovarian cancer responded to platinum-based chemotherapy.
The nod drew attention because it was granted for “all-comers” of ovarian cancer. Zejula made it possible to use the targeted therapy for all advanced ovarian cancer patients, not just those with particular genetic mutations such as BRCA or HRD.
The approval for Zejula was based on the phase-3 Prima study, which showed that the Zejula monotherapy reduced the risk of disease progression and death by 38 percent, compared to the placebo.
Lynparza also proved that its combination with bevacizumab reduced the risk of disease progression and death by 41 percent, compared to bevacizumab alone, in the all-comer group in the PAOLA-1 study. However, the approval was allowed for those with HRD expression only.
Thus, AstraZeneca aims to maximize Zejula’s therapeutic effect by presenting various treatment options such as monotherapy and combo therapy for the primary maintenance treatment despite limited conditions involving BRCA and HRD.
In contrast, Takeda seeks to provide targeted therapy for all progressive ovarian cancer patients, regardless of genetic mutations.
As the only targeted therapy as a maintenance treatment in ovarian cancer, PARP inhibitors have contributed to delaying the cancer recurrence. However, the limitations of reimbursement criteria allowed only some of the patients to enjoy therapeutic benefits, industry watchers said.
In Korea, Lynparza won the license for the first-line maintenance therapy for progressive ovarian cancer in patients with BRCA mutation. For the secondary maintenance treatment, it was permitted to be used for all-comers.
Zejula was authorized as a secondary maintenance treatment for all-comers, and as the tertiary or higher monotherapy for those with BRCA mutation or HRD.
However, the national health insurance benefit is available for secondary maintenance therapy for patients with BRCA mutation only. Thus, 80-85 percent of the ovarian cancer patients cannot receive the PARP inhibitor treatment.
“In Korea, about 2,800 cases of ovarian cancer occur annually. If we include fallopian tube cancer or peritoneal cancer, the number goes up to more than 3,100,” said Lee Jeong-yoon, a professor of the Obstetrics and Gynecology Department of Severance Hospital. “Ovarian cancer has shown poor survival and frequent recurrence over the past 20 years. If recurrence continues, it can shorten progression-free survival.”
He emphasized that PARP inhibitors, which became the first targeted therapy for ovarian cancer, have put off the recurrence and improved survival in ovarian cancer patients with poor prognosis.
AstraZeneca Korea recently changed the form of Lynparza from capsule to tablet to expand reimbursement, and Takeda Pharmaceuticals Korea also sought broader insurance coverage for Zejula.