GlaxoSmithKline (GSK) has announced plans to buy Waltham, MA–based biotech Tesaro, maker of the once-daily oral PARP inhibitor niraparib (Zejula), in a deal valued at $5.1 billion.

GlaxoSmithKline (GSK) announced plans in December to buy Waltham, MA–based biotech Tesaro, maker of the once-daily oral PARP inhibitor niraparib (Zejula), in a deal valued at $5.1 billion.

The acquisition will bring GSK into an increasingly crowded field of PARP-targeting drugs—one that has seen sluggish sales and slower-than-expected use among oncologists, because maintenance therapy is still relatively new in ovarian cancer. Yet company executives are confident that they can turn niraparib into a commercial success, both as a monotherapy and in combination with other agents for treating not only gynecologic cancers, but also other tumor types.

“Our strong belief is that PARP inhibitors are important medicines that have been underappreciated in terms of the impact they can have on cancer patients,” says GSK president and chief scientific officer Hal Barron, MD.

Four PARP inhibitors are currently available for patients with advanced breast and gynecologic cancers. The market leader, olaparib (Lynparza; AstraZeneca), earned FDA approval in December 2014 as maintenance therapy for ovarian cancer; approvals for fallopian tube, peritoneal, and breast cancers soon followed. Then came rucaparib (Rubraca; Clovis Oncology) and niraparib—approved in December 2016 and in March 2017, respectively—for recurrent ovarian, fallopian tube, and peritoneal cancers, also as maintenance therapy.

In October, talazoparib (Talzenna; Pfizer) joined the formulary with an approval for germline BRCA-mutant, HER2-negative advanced breast cancer. Meanwhile, international pivotal phase III trials for AbbVie's veliparib and, in China, BeiGene's pamiparib in ovarian cancer are ongoing.

Many of these PARP inhibitors are also being evaluated in other tumor types, including cancers of the stomach, colon, bladder, and brain. Trials are ongoing with niraparib, for example, in patients with prostate cancer, non–small cell lung cancer, Ewing sarcoma, breast cancer, and for the management of certain ovarian cancers.

In general, says Premal Thaker, MD, of Washington University School of Medicine in St. Louis, MO, the approved PARP inhibitors all work about equally well in patients with ovarian cancer. The main differences boil down to side effects and dosing regimens. Niraparib seems to cause higher rates of thrombocytopenia and neutropenia than other agents—“but then it also has the convenience of once-a-day dosing, which does make it more useable and patient-friendly,” she says. By contrast, both olaparib and rucaparib must be taken twice a day.

Initially, PARP inhibitors were approved only for women whose platinum chemotherapy–sensitive disease featured germline BRCA1/2 mutations or homologous recombination deficiency—defects that increase genetic instability and make tumors intrinsically sensitive to the drugs. Niraparib was then greenlighted without requiring the use of a molecular biomarker, followed soon after by a similar expanded indication for olaparib.

Both olaparib and niraparib are now in phase III trials as first-line maintenance therapy for ovarian cancer. Preliminary data with olaparib suggest that this treatment strategy can delay the progression of germline BRCA-mutant disease.

Phase II combination trials in ovarian cancer, pairing niraparib with the angiogenesis blocker bevacizumab (Avastin; Genentech) or the PD-1 inhibitor pembrolizumab (Keytruda; Merck), are also ongoing. As well, by acquiring Tesaro, GSK will gain the biotech's portfolio of early-phase immune checkpoint inhibitors, including a PD-1 inhibitor called dostarlimab, and antibodies directed at TIM3 and LAG3. –Elie Dolgin

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