BARCELONA—GlaxoSmithKline aimed high with its latest Zejula study: It wanted to prove the PARP inhibitor could fend off ovarian cancer in women who’d responded to one round of platinum chemotherapy—all women, not just those with the genetic mutation that makes tumors most susceptible to treatments in its class.
The drug, which GSK acquired in its $5.1 billion Tesaro buyout, stopped cancer in its tracks, cutting the risk of disease progression or death by 38% across the spectrum of ovarian cancer patients, and by more than that in a key patient group, according to data released here at the European Society for Medical Oncology meeting.
“From a treatment perspective, we can now say this works in all patients regardless of subgroup,” said Axel Hoos, SVP and oncology head at GSK, in an interview ahead of the data release. “All can benefit.”
That’s a distinction its rivals in the competitive PARP inhibitor class can’t boast, at least on the monotherapy side; archrival Lynparza from AstraZeneca and Merck put up data at ESMO Saturday showing the drug combined with Avastin could keep cancer at bay in all-comers, too.
And the new data could be enough for GSK to carve out a niche for itself despite Lynparza's commanding lead; the AZ/Merck drug delivered first-half 2019 sales of $520 million to Zejula’s £99 million.
In the phase 3 study, dubbed Prima, numbers looked best for patients with a BRCA mutation—the risk of progression dropped by 60% for that group—but the results in so-called “wild type” tumors also topped placebo by wide margins. A 50% reduction in risk for wild-type BRCA patients whose tumors had homologous recombination deficiencies (HRD), for one, and 32% for women with neither BRCA mutations nor HRD.
The recurrence rate in ovarian cancer can be intimidating, Hoos pointed out, so GSK is “very proud of these results,” he said. “If we are able to give patients a pill and reduce the risk of recurrence by these numbers—anywhere from 32% to 60%—yes, that’s a big deal.”
And if Zejula wins a new approval based on these numbers, doctors wouldn’t have to screen patients for BRCA mutations to prescribe Zejula, Hoos pointed out. As the maker of any targeted drug knows, diagnostic testing—or the lack of it in routine practice—can be a big hurdle, and it’s likely one reason why PARP inhibitors aren’t used more broadly.
For GSK, the no-test-required angle could give it an advantage over Lynparza, whose first-line maintenance approval—granted quite speedily after impressive data released at last year’s ESMO meeting—for now applies only to women with BRCA mutations. In the Solo-1 study, which only enrolled BRCA-positive patients, Lynparza cut the risk of disease progression or death by a whopping 70%.
As of Saturday, Lynparza's combo data with Avastin has now shown it can cut the risk of disease progression or death by 41% regardless of BRCA status—but that comes with Avastin's well-known side effects.
Jefferies analyst Peter Welford figures Zejula could carve out its own niche in women without the BRCA mutation, particularly those who are HR-deficient. That’s 35% of ovarian cancer patients, Welford said when the top-line Zejula data were released—and more than twice the fraction with BRCA tumors (15%).
The Prima study hasn’t yet shown Zejula can help first-line patients live longer, but the trend in that direction is encouraging, Hoos said.
An interim analysis “numerically favored” Zejula across the study, GSK said in its data release, noting that the data aren’t yet mature. Among HR-deficient patients, 91% of those taking Zejula were alive after two years compared with 85% for placebo, the analysis showed. In the HR-proficient group, 81% of Zejula patients were alive at the two-year mark, compared with 59% of those in the placebo arm.
Right now, the five-year survival rate for ovarian cancer is less than 50%, GSK noted in its data release.
GSK is enrolling a study testing Zejula alongside its PD-1 checkpoint inhibitor, dostarlimab, in ovarian cancer, again hoping to show a benefit for all ovarian cancer patients regardless of BRCA status. And it’s working on some follow-up analyses from Prima, including one examining dosing based on a patient’s weight that could go public before the end of the year.