Until last week, there were no treatments approved to keep ovarian cancer away in women who'd responded to an initial round of chemo but didn’t have a BRCA mutation.
Now there are two.
AstraZeneca and Merck’s Lynparza, in tandem with Roche’s Avastin, nabbed an FDA green light Friday to treat those women, and those with BRCA mutations, too. The approval follows fast on the heels of the agency’s nod for GlaxoSmithKline’s Zejula in the same population, which came last Wednesday.
Lynparza's approval isn't as broad as Zejula's, though. The FDA didn't clear it for use in patients without homologous recombination deficiencies (HRD), a group for which the Lynparza-Avastin combo cut the risk of disease progression or death by just 8%. About half of women with advanced ovarian cancer have an HRD-positive tumor, AstraZeneca said.
"We are somewhat surprised by the HRD restriction placed in the Lynparza label since AZN (OP) management previously communicated they would file for approval in the intent-to-treat (ITT) population," Leerink Partners analyst Geoffrey Porges wrote in a Friday note to clients, adding that "Lynparza’s HRD-only approval further affirms our positive Zejula outlook."
Regulators based their Lynparza decision on data showing that patients taking the drug went a median 37.2 months without seeing their disease worsen, versus 17.7 months for women receiving Avastin plus placebo. AZ and Merck unveiled those results at last fall’s European Society for Medical Oncology annual meeting, where GSK also trumpeted the data that supported Zejula’s recent go-ahead.
Now, the two regimens will go head-to-head in the market, except in HRD-negative patients, where Zejula will be facing down solo Avastin. "We have modeled Zejula as having the best commercial opportunity in the HRD- cohort, where the drug will need to compete with Avastin to gain market share," Leerink Partners analyst Andrew Berens wrote in his own Friday note to clients.
GSK's contender will also wield an advantage in the convenience department. Zejula, a pill, is taken on its own, without the challenges that come along with an Avastin infusion—particularly during a pandemic, when patients are trying to stay home as much as possible.
Adding a second drug to the mix can also introduce extra toxicity, Axel Hoos, SVP and oncology head at GSK, said in a recent interview.
But at ESMO, Dave Fredrickson, EVP and global head of AstraZeneca’s oncology business unit, stressed that the toxicity from the two drugs was “non-overlapping,” a factor he called “the most key.”
“Certainly there’s a different side effect profile than having Lynparza by itself, but we think the benefit-risk on this is clear” for the combo, he said at the time.
Meanwhile, Berens expects Lynparza to hang onto its current lead in BRCA-positive patients and for AstraZeneca and Merck to use their "numerically better efficacy" in other HRD-positive patients—the Lynparza-Avastin pairing kept disease at bay for a median 28.1 months in that group, versus Zejula's 19.6 months—to "encourage clinicians to test for HRD status," he wrote.
While only time will tell which regimen will take the lead in the market, Lynparza safely holds the PARP class lead when it comes to indication count. So far, it’s been the first in its field into ovarian, breast, and pancreatic cancer, and it’s racing Clovis Oncology’s Rubraca to enter the prostate cancer field, too.