AstraZeneca, GSK's cancer rival Clovis quietly unveils crippling FDA delay as its troubles deepen

Declining sales of its lead cancer drug, a need to raise additional capital and a 30% stock price plunge depict the nightmare Clovis Oncology is living through right now. But that’s not all.

In a quarterly filing published Thursday, Clovis Oncology quietly revealed (PDF) that the FDA has asked for additional data for the company’s bid to expand its sole commercial product, PARP inhibitor Rubraca, as a maintenance treatment in newly diagnosed ovarian cancer patients who’ve responded to an initial round of chemotherapy.

During discussions on Tuesday and Wednesday, the FDA made clear that it wants to see data on whether Rubraca can extend patients’ lives. By Clovis’ estimates, it’ll take an additional two years to get those overall survival data to the agency. Problem is, the company might not survive that long.

Clovis reported positive results in March showing that the drug bested placebo at preventing disease progression or death across a broad patient population in the first-line maintenance setting, a key battleground for PARP inhibitors. The phase 3 Athena-Mono trial has therefore met its primary endpoint.

Before Clovis, AstraZeneca and partner Merck & Co. won an FDA approval for Lynparza, and GlaxoSmithKline for its Zejula, in the same first-line maintenance ovarian cancer setting based progression-free survival data. But now the FDA is “placing increasing emphasis on overall survival,” Clovis noted, pointing to the agency’s recent crackdown on the PI3K drug class over safety concerns.

Specifically, the FDA has told Clovis that it shouldn’t file for approval until the Athena-Mono trial has accrued at least 50% pre-specified death events for an overall survival analysis. The study is currently only halfway there, with overall survival findings about 25% mature, Clovis said.

Clovis could go against FDA’s advice and file anyway, but the agency warned that it would hold an advisory committee meeting to discuss the submission. 

At the time Clovis touted that disease progression win, the death risks between Rubraca and placebo were basically the same in both the entire trial population and a subgroup of patients with homologous recombination deficiency (HRD) tumors. Patients with HRD-positive tumors typically respond well to PARP inhibitors like Rubraca.

What’s more, because patients may go on to receive multiple later-line therapies that could impact survival, it’s inherently difficult for a drug in first-line treatment to show a survival benefit. That means, even if Clovis waits those two years, it might still not get a clear overall survival signal.

To make things worse, the FDA also took into consideration findings from the Ariel4 postmarketing trial, which compared Rubraca with chemotherapy in patients with previously treated BRCA-mutated ovarian cancer. There, Rubraca showed an advantage at slowing disease progression but seemed to perform worse at prolonging lives.

Based on the findings, the European Medicines Agency has started a new review of Rubraca’s benefit-risk profile and advises doctors not to start new patients on the third-line indication. Clovis also anticipates a dialogue with the FDA on the findings, CEO Patrick Mahaffy said during the company’s first-quarter earnings call Wednesday.

Since its initial FDA accelerated approval in third-line ovarian cancer, Rubraca has suffered from tough competition from Lynparza and Zejula. In the first quarter, Rubraca brought in sales of $34.2 million, down 10% over the same period last year and down 5% over the fourth quarter of 2021. Clovis attributed the lackluster performance to COVID-19. But by comparison, both Lynparza and Zejula posted year-over-year growth.

First-line maintenance ovarian cancer could be Rubraca’s last chance at any meaningful sales, or the drug “risks becoming increasingly clinically irrelevant” in the PARP market, SVB Securities analyst Andrew Berens has said.

Clovis management has touted the indication as a potential inflection point for Rubraca. But for now, Clovis will likely have to wait longer as its Big Pharma rivals solidify their leads.

Rubraca’s Athena trial programs are being funded through a non-dilutive clinical trial financing deal Clovis signed with TPG Sixth Street Partners in May 2019. As of the end of March, Clovis had burned $156.4 million, leaving only $18.6 million available for draw.

In the first quarter, Clovis reported a net loss of $60.2 million and said it held $122.2 million in cash. As a result, the company recognizes that it will “need to raise additional capital in the near term to fund its operating plan for the next 12 months and to continue” as a functional business, it said in its first-quarter report.

Clovis’ stock price has plummeted 30% since Wednesday’s earnings report. On the company’s earnings call, only one analyst asked a question.