- GlaxoSmithKline may be closing the gap between its targeted cancer therapy Zejula and a rival product from fellow U.K. drugmaker AstraZeneca, according to a clinical readout disclosed Monday.
- Topline results from the Phase 3 PRIMA study show GSK's Zejula, which inhibits a DNA repair enzyme called PARP, significantly improved progression free survival over placebo when used as a first-line maintenance treatment following platinum-based chemotherapy.
- AstraZeneca's Lynparza is also a PARP inhibitor, and the only one to have gained U.S. approval in the first-line maintenance setting for ovarian cancer, though that approval is for patients with specific genetic mutations. Zejula, meanwhile, is cleared as a maintenance treatment for patients with recurrent ovarian cancer, regardless of whether they have such mutations.
PARP inhibitors are targeted cancer therapies that have been most useful in patients with BRCA mutations, which impair the ability of cells to repair their DNA. The idea behind drugs like Zejula (niraparib), Lynparza (olaparib) and Clovis Oncology's Rubraca (rucaparib) is that, by also blocking the PARP pathway, cancer cells aren't able to repair themselves after chemotherapy and therefore die.
But BRCA mutations aren't terribly common. The Dana Farber Cancer Institute estimates about 1 in every 500 U.S. women have either a BRCA1 or BRCA2 mutation.
As such, pharmaceutical companies have been investigating whether PARP drugs can offer health benefits in the wider population. Zejula, Lynparza and Rubraca, for instance, are all indicated as maintenance therapies for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer regardless of a patient's BRCA status.
Lynparza remains ahead of the other two both in terms of sales and the breadth of its label. In December, it received a key approval for the frontline maintenance of BRCA-mutated patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.
GSK, however, argues there needs to be more first-line options. Hal Barron, head of pharma giant's R&D operations, said just about 15% of the nearly 300,000 women diagnosed with ovarian cancer each year are currently eligible for PARP inhibitors as an initial treatment.
PRIMA enrolled an estimated 620 patients with Stage 3 or 4 ovarian, fallopian tube or primary peritoneal cancer. While the company expects to present more detailed results at a later scientific conference, hitting the trial's primary endpoint drummed up some positive investor sentiment. GSK shares were up about 1.5% in late morning trading Monday.
"GSK's PRIMA trial provides the first evidence that PARP [inhibitors] convey activity in non-biomarker defined patients in the [first-line] maintenance setting," RBC Capital Markets analyst Kennen MacKay wrote in a July 15 note about Clovis.
Clovis is also looking to branch into the first-line treatment of ovarian cancer, but lags behind its competitors. The first-line has been an attractive target for all three companies, due in part to market challenges in the second-line setting.