It’s no secret that so-called PARP inhibitors, a new class of cancer drugs, have struggled to gain traction commercially, even as they’ve shown promise treating multiple tumor types. But today brings news that could bolster the future prospect of PARP blockers: one of them, a drug known as olaparib (Lynparza) from AstraZeneca and partner Merck, may work treating pancreatic cancer, a particularly fast-moving, deadly tumor with limited treatment options.
AstraZeneca (NYSE: [[ticker:AZN]]) and Merck (NYSE: [[ticker:MRK]]) said today that olaparib has met its main goal in a Phase 3 study in 154 pancreatic cancer patients whose tumors have a mutated BRCA gene and whose disease had yet to recur after chemotherapy. Olaparib, when given as a maintenance therapy, helped keep cancer from spreading longer than placebo.
It’s worth noting that the two didn’t disclose the specific results of the trial, known as POLO, so the magnitude of that benefit is unclear—as is whether the drug helped pancreatic cancer patients live longer, a key secondary study goal. Those details will be shared at a future medical meeting, and they’ll be particularly important. Pancreatic cancer is an uncommon but particularly deadly tumor because it’s hard to detect early, moves very fast, and can’t be surgically removed. The disease is estimated to kill 45,750 Americans in 2019 and was the fourth-leading cause of cancer-related death last year, according to the American Cancer Society.
POLO marks the first time PARP blockers have succeeded in a Phase 3 trial beyond ovarian and breast cancer. Thus, the key details from POLO may help broaden the reach of PARP inhibitors, which block an enzyme, poly (ADP-ribose) polymerase, which tumors use to repair DNA damage.
After some initial clinical setbacks, four PARP blockers have won FDA approval since 2014: olaparib, niraparib (developed by Tesaro but now owned by GlaxoSmithKline) , Clovis Oncology’s (NASDAQ: [[ticker:CLVS]]) rucaparib (Rubraca), and most recently in October, Pfizer’s (NYSE: [[ticker:PFE]]) talazoparib (Talzenna).
Olaparib reached the market first, and at least so far, has claimed dominance over its rivals. It was first approved for patients with certain forms of ovarian cancer and defective BRCA genes who have failed multiple chemo regimens. Niraparib and rucaparib followed, both as maintenance therapies to delay ovarian cancer’s recurrence after chemotherapy. Beyond ovarian cancer, PARPs have begun to show real benefits for patients with other tumors as well. Both olaparib and talazoparib have won approvals for breast cancer.
So far, however, these drugs have yet to meet their high commercial expectations. AstraZeneca’s drug has established itself as the leader, with $647 million in sales in 2018, though that total consists of both breast and ovarian cancer sales. The others have lagged behind: rucaparib, for instance, generated close to $96 million in 2018. As Leerink analyst Andrew Berens wrote in a research note last year, developers have had “persistent challenges in growing the market” for PARP inhibitors, particularly in getting doctors to prescribe them as maintenance agents.
Still, drug developers continue to believe in their upside and are trying to broaden their reach by testing these drugs alone and in combination with others in lung, prostate, and other cancers. GlaxoSmithKline (NYSE: [[ticker:GSK]]) paid $5.1 billion for Tesaro in December to get in on the PARP battle and test niraparib in multiple tumor types; its chief scientific officer, Hal Barron, called PARP blockers “under appreciated” at the time. And AstraZeneca and Merck are testing olaparib in several cancers as well.
“The results of POLO provide further evidence of the clinical benefit of Lynparza across a variety of BRCA-mutated tumour types. We will discuss these results with global health authorities as soon as possible,” said AstraZeneca executive vice president of R&D, Jose Baselga, in a statement.
Pancreatic cancer cells image from the National Cancer Institute
