Clovis Oncology received a short-cut approval from the FDA last year for its ovarian cancer drug that treats women with the common BRCA genetic mutation. Clovis (NASDAQ: CLVS) said Monday it now has evidence that the drug, rucaparib (Rubaca), can treat a wider swath of patients, and it will ask the FDA for approval this year.
The Boulder, CO, company reported that women in the 564-patient, double-blinded ARIEL3 study fared better on rucaparib than on placebo, whether or not they had tumors driven by the BRCA mutation. The trial studied women who were already faring well from previous chemotherapy treatments. The main goal was to measure how long rucaparib could keep their cancer at bay—what’s known as progression-free survival.
“We clearly are going to apply for approval for the ‘all-comers’ population, which would allow physicians if granted to prescribe rucaparib without [BRCA] testing,” said Clovis CEO Patrick Mahaffy today.
Ovarian cancer will kill about 14,000 U.S. women this year and account for 2.3 percent of all cancer deaths in the U.S. in 2017, according to National Cancer Institute estimates. Like breast cancer, a significant portion of those cancers are driven by the BRCA mutation—about 15 to 20 percent, according to the FDA. Standard treatment is surgery followed by chemotherapy, but Clovis and others are competing to establish a new class of drugs known as PARP inhibitors as part of the treatment mix.
PARP is shorthand for poly ADP-ribose polymerases, enzymes that help cancer respond to DNA damage. Blocking their activity hampers the ability of cancer cells to repair their DNA after the DNA has been damaged by, say, chemotherapy. AstraZeneca (NYSE: AZN) received the first ovarian cancer approval for a drug in this new class in 2014. Tesaro (NASDAQ: TSRO), the subject of buyout rumors, followed with an FDA approval for its PARP blocker earlier this year.
In the new ARIEL3 data released today, the 164-patient BRCA group fared the best, with 16.6 months of median progression-free survival, or PFS, compared to 5.4 months in the placebo group.
A larger subset of 354 patients whose disease is driven by a general failure of cells to repair themselves, which include those with BRCA mutations, also fared well with 13.6 months of PFS. Finally, everyone who received rucaparib in the study regardless of BRCA status also fared better than placebo, with 10.8 months of PFS, double the placebo rate.
Those data came from doctors working alongside Clovis. The firm said an independent review board also crunched the data and came up with data even more favorable to rucaparib.
The most prominent side effect was anemia, which affected 19 percent of patients on rucapirib. A fuller set of data from Clovis will come later this year at a medical conference.
Clovis said it would use the data to ask for FDA approval of rucaparib in patients who have already been treated with two or more types of chemotherapy. The company has a rocky track record with drug approvals. Before rucaparib received a conditional approval last December, Clovis had brought its lung cancer drug rociletinib to the FDA for review, then received a rejection one month before the agency’s deadline for a decision. Clovis announced it was pulling the plug on rociletinib, the end of a long chain of events that raised investor ire and drew the attention of law enforcement.
The rociletinib controversy continues. Clovis also disclosed Monday that it has earmarked $142 million to settle a class-action lawsuit stemming from its promotion of rociletinib in the run-up to the FDA’s rejection. The proposed settlement payout would mainly come in the form of Clovis shares worth $117 million.
In its disclosure, the company maintains it did nothing wrong. Federal agencies including the Securities and Exchange Commission and Justice Department continue to investigate the company, according to the announcement.
All told, the ARIEL3 data and the proposed settlement pushed Clovis shares up nearly 50 percent to $88.48 in mid-day trading.
PARP blockers have had their share of ups and downs, but after some high-profile setbacks, AstraZeneca won FDA approval of the first PARP-blocking drug, olaparib (Lynparza) in 2014. Like rucaparib, olaparib was approved for patients with certain forms of ovarian cancer and defective BRCA genes who have failed multiple chemotherapy regimens. Tesaro’s niraparib was approved earlier this year for ovarian cancer patients who have failed chemotherapy but, unlike its competitors, does not require a companion diagnostic test for the BRCA mutation.
Tesaro shares are down nearly 1.5 percent to $142.21.