Under siege from rival drugs by GlaxoSmithKline and AstraZeneca, Clovis Oncology’s Rubraca faces an existential crisis. But the biotech hopes a new win in a broad ovarian cancer patient population—and a possible FDA nod—will put its med in a better position alongside Big Pharma competitors.
Rubraca significantly bested placebo at preventing disease progression or death in newly diagnosed ovarian cancer patients who had responded to an initial round of chemotherapy, Clovis said Thursday. Based on the positive readout, Clovis plans to file for an FDA approval in the second quarter.
In an important showing that could determine Rubraca’s value in the PARP inhibitor market, the drug showed a tumor progression benefit in all patients, including those whose tumors didn’t have homologous recombination deficiencies (HRD).
Clovis’ stock price jumped over 50% at the news Thursday morning.
Clovis CEO Patrick Mahaffy was quick to point out that the broadly inclusive win, from the phase 3 Athena-Mono study, “exceeded” the company’s expectations. The company had fully expected that Rubraca would work in patients with BRCA mutations and the broader HRD-positive population, where PARP inhibitors have historically worked best, he said during a conference call Thursday. But the HRD-negative population was more of a wild card.
Still, because the new Rubraca data come two years after FDA nods for GSK’s Zejula and AZ and Merck & Co.’s Lynparza in the first-line maintenance setting, the Clovis drug's market potential remains uncertain.
The latest data at least give Rubraca an edge over Lynparza, currently the market-leading PARP inhibitor. Lynparza’s FDA nod in first-line maintenance ovarian cancer is confined to patients with HRD, and the drug needs to be used alongside Roche’s Avastin in patients without BRCA mutations.
In Athena-Mono, Rubraca monotherapy pared down the risk of disease progression or death by 48% compared with placebo in all patients regardless of tumor biomarker status. Patients taking the drug went 20.2 months without disease progression versus 9.2 months for placebo.
In an exploratory subgroup analysis, Rubraca reduced that risk by 35% in patients without HRD. Those patients who took Rubraca lived a median 12.1 months free of progression versus 9.1 months for placebo.
HRD-negative patients represent about half of the ovarian cancer population.
Rubraca’s data also look competitive against Zejula, which is currently the only PARP inhibitor carrying a broad, all-comers nod in the first-line maintenance setting. In Zejula’s own phase 3 trial, dubbed Prima, the GSK med reduced the risk of disease progression or death by 38% in the overall population, and 32% in HRD-negative patients.
Despite the intrinsic problems of cross-trial comparison, industry watchers do it anyway to understand the competitive landscape. Both Zejula’s Prima and Rubraca’s Athena-Mono enrolled roughly 50% of HRD-negative patients, but the Zejula trial enrolled a higher percentage of BRCA-mutant patients, who typically respond best to PARP inhibition.
Athena-Mono is a go-big-or-go-home readout for Rubraca. As SVB Leerink analyst Andrew Berens, M.D., had put it in August, the Clovis drug risked “clinical irrelevance,” given that it has been “a distant follower in the most commercially and clinically relevant PARP opportunities.” At that time, Berens questioned that even a positive Athena readout would “tip the scale enough for Rubraca to gain traction in the 1L setting versus Lynparza and Zejula.”
Both Lynparza and Zejula posted double-digit sales growth last year, with Lynparza leading the market at $2.35 billion in sales for AZ. Zejula reeled in 395 million pounds ($520 million) thanks to a 22% year-over-year growth at constant currencies.
By contrast, Rubraca sales dropped 10% to $149 million last year as Clovis blamed the ongoing COVID-19 pandemic for the lackluster performance. Rubraca has been approved in second-line maintenance treatment of ovarian cancer, third-line BRCA-mutant ovarian cancer and BRCA-mutant castration-resistant prostate cancer.
Clovis believes it has another opportunity to lock in first-line maintenance market share. The other part of the Athena clinical program, called Athena-Combo, is testing whether adding Bristol Myers Squibb’s PD-1 inhibitor Opdivo could further improve upon Rubraca monotherapy. The readout from that comparison is now delayed into the first quarter next year as the accrual of disease progression or death events was slower than expected.