Since late 2018, women with ovarian cancer who responded to an initial round of chemo have been eligible to receive a PARP inhibitor, but only if they had a BRCA mutation. Now, GlaxoSmithKline’s Zejula has changed that.
The FDA on Wednesday green-lighted (PDF) the drug as a first-line maintenance therapy for all women, regardless of BRCA mutation status. It’s a move that vaults Zejula ahead of AstraZeneca and Merck’s Lynparza, its in-class competitor, in a key market—at least for now.
Regulators based their decision on data from the phase 3 Prima study, unveiled at September’s European Society for Medical Oncology (ESMO) annual meeting, which showed Zejula could slash patients’ risk of disease progression or death by 38%.
The approval marks a “simplification of the treatment paradigm” and “quite a positive advance for patients,” Axel Hoos, SVP and oncology head at GSK, said.
“Particularly now, in the COVID-19 environment where it’s harder for patients to go to the doctor and harder to receive an infusion or even do surgery—you just take a pill, and on top of that you don’t need to undergo testing to find out if you are eligible for this based on mutation. Everyone can benefit,” he said.
For now, Zejula is the only PARP inhibitor cleared in the all-comer population for first-line maintenance, giving it a leg up over the AZ-Merck team, whose Lynparza is restricted to the BRCA-mutated group. But those two partners, also at ESMO, presented positive all-comer study results from Lynparza paired with Roche’s Avastin.
One key difference that could set Zejula apart, even if AstraZeneca and Merck land an all-comer go-ahead of their own?
Zejula is taken solo, avoiding the “added complexity that comes with adding a second drug,” Hoos said, pointing to additional toxicity and the fact that Avastin is an infusion rather than a pill.
What’s more, Zejula spurred significant benefits in patients across three key subgroups: those with BRCA mutations, those whose tumors had homologous recombination deficiencies (HRD), and those with neither BRCA mutations nor HRD. In the Lynparza-Avastin win, big benefits in the first two groups carried the study to a positive outcome, Hoos pointed out. But in the HRD-negative group, the combo cut the risk of disease progression or death by just 8%.
For now, though, GSK won’t have to worry about the Lynparza-Avastin duo; it's still waiting for a thumbs up from the FDA after winning the agency’s priority review status in January.
Instead, the British drugmaker will be focused on getting the word on Zejula out to doctors, many of whom have been slower to adopt PARP inhibitors than industry watchers have expected, given the drugs’ stellar efficacy data.
For Zejula, “the benefit is there, and it’s universal, but physicians just need to see it. They need to have an opportunity to see the drug and see the benefit in their own patients,” Hoos said. “We hope that the approval … will give us an opportunity to make this as visible as possible.”