After the PARP inhibitor showdown at ESMO this weekend between GlaxoSmithKline’s Zejula and AstraZeneca and Merck & Co.’s Lynparza, industry watchers declared it difficult to tell who won this round of the data battle. But another company should definitely feel the pressure, analysts say, and that's Clovis Oncology.
When GSK unveiled its $5.1 billion deal for Zejula maker Tesaro, industry watchers figured it should read well across the entire PARP class, especially for the other underdog, Clovis’ Rubraca. But now that the Big Pharma players have turned in what could be game-changing clinical results, at least two groups of analysts are worried for the small firm.
After updates for Zejula and Lynparza, competition for Clovis is “increasing in frontline ovarian cancer, prostate cancer and breast cancer,” SVB Leerink analysts wrote in a Tuesday note to clients. Noting the established ovarian cancer arena as already hard for Rubraca to play catch-up in, J.P.Morgan analysts, in an investors’ note Monday, also found Lynparza’s new prostate cancer data “incrementally negative to Clovis.”
A recap of what happened at the European Society for Medical Oncology annual meeting: In the phase 3 Profound trial of previously treated metastatic castration-resistant prostate cancer (mCRPC) patients, Lynparza significantly extended the time to disease worsening compared with new hormonal drugs such as Johnson & Johnson’s Zytiga or Pfizer and Astellas’ Xtandi. Men with BRCA or ATM mutations went 7.4 months without progression on Lynparza, versus 3.6 months among those on other drugs.
Although Lynparza’s benefit seems most pronounced in those with BRCA2 mutations, SVB Leerink’s Andrew Berens said, because the trial combined patients in a single cohort, his team believes the AZ-Merck drug could still snag an inclusive label, “potentially allowing for broader use beyond the expanded Rubraca label, which is likely to be limited to BRCA+ patients.”
Clovis did also come up with its own prostate update, but it was from a single-arm study, and the data were “largely in line with” what Clovis reported last year, J.P. Morgan’s Cory Kasimov noted, that the drug triggered an overall response rate of 44% in the BRCA-mutated cohort.
AZ-Merck and Clovis are now vying to be first-to-market in mCRPC, both eyeing data submissions this year and potential approvals in 2020. But the slight potential timing difference might not matter so much, as Lynparza’s progression-free survival data from a randomized head-to-head phase 3 study represent a huge advantage over Rubraca’s phase 2 response rate data when it comes to selling the drugs, both analyst teams argued.
Lynparza’s data are “likely to lead to preferential uptake and reimbursement, particularly in Europe where value-based government payers have shown preference for randomized data vs. single-arm studies,” Berens said.
In ovarian cancer—the more established PARP battleground—Clovis is also facing challenges in a class-wide push into the broader, first-line maintenance population.
GSK touted results from the Prima study, showing Zejula alone could cut the risk of disease progression or death by 38% across ovarian cancer patients who’d responded to one round of platinum chemo. Those with a BRCA mutation saw a reduction of 60%; wild-type BRCA patients with homologous recombination deficiencies (HRD) had a 50% drop in risk, and HRD-negative experienced a 32% fall.
Lynparza currently leads as the only PARP drug with a first-line maintenance approval, which it picked up after showing it could cut the risk of disease progression or death by a whopping 70%. That go-ahead only applies to women with BRCA mutations, but AstraZeneca and Merck are not stopping there. Investigators from the Paola-1 study found that adding Lynparza to Roche’s Avastin slashed the risk of disease progression by 41% for all patients, regardless of BRCA status, over Avastin alone.
Rubraca, meanwhile, doesn’t expect its own front-line maintenance results until the phase 3 Athena trial reads out in 2021. There is one silver lining, though, Berens noted: Athena, combining Rubraca with Bristol-Myers Squibb’s Opdivo, could be the first pivotal data for a PARP/PD-1 combo in ovarian cancer maintenance.
Rubraca sales have been suffering, totaling only $33 million in the second quarter. In the same period, Zejula returned £57 million ($70 million) and could enjoy better results now with recent buyer GSK’s marketing power. Both were no match to Lynparza’s $520 million, as it continues to expand in ovarian and breast cancer around the world.