|Clovis CEO Patrick Mahaffy|
Over the weekend, Clovis Oncology ($CLVS) took another big step toward its near-term goal of launching commercial operations, with plans to take pharma giant AstraZeneca ($AZN) head-on with two key franchise showdowns. The Boulder, CO-based biotech posted positive data from a mid-stage study of its ovarian cancer drug rucaparib at ASCO, while adding new--though less impressive--data to back up its lead drug for non-small cell lung cancer.
Lower progression-free survival rates in lung cancer may lead to some unfavorable comparisons with AstraZeneca's AZD9291 and come back to haunt Clovis as analysts weigh in on rociletinib. That may explain an 8% drop in the company's volatile share price in early trading on Monday.
But first up this weekend was Clovis's rucaparib, a rival to AstraZeneca's olaparib, which was approved recently as Lynparza.
Staking out its claim that rucaparib should be a best-in-class PARP inhibitor pick for physicians, Clovis outlined evidence that demonstrated tumor shrinkage in 32 of 39 patients--an 82% response rate. The median progression-free survival rate was 9.4 months in the treatment-resistant BRCA mutant population, while a group with "BRCA-like" profiles demonstrated a 45% response and a 7.1-month PFS rate.
In non-mutant cases, the average PFS rate was 3.7 months. A total of 204 patients were recruited for the Ariel2 study.
"We have really learned how to select a patient pop that responds to a PARP inhibitor," says Clovis CEO Patrick Mahaffy, adding that the BRCA population amounts to 25% of the ovarian cancer patient population, while BRCA-like patients would boost that to 60%, greatly expanding its potential market reach, provided it can go on to win an approval.
The plan now is to push clinical work on the drug and focus on a new drug application in the middle of next year, says Mahaffy, who's also eager to follow up with combination studies that have the potential to double survival rates for cancer patients, with an eye to expanding its work into other solid tumor types.
Mahaffy has good reason to be confident. AstraZeneca won an accelerated approval for olaparib last fall based on a 34% response rate among germline BRCA ovarian cancer patients who had failed three prior drugs. Initially, FDA advisers turned thumbs-down on the drug, but the pharma giant came back with new information that satisfied the agency. In addition, rucaparib--like its lead drug rociletinib, which also faces a rival at AstraZeneca--has won the FDA's "breakthrough" designation, providing an open door to regulators.
Rociletinib (CO-1686) is closer to an FDA filing, and may be in for closer scrutiny among analysts. Clovis' Phase II data for roci demonstrated a median progression-free survival rate of 8 months among heavily pre-treated EGFR-mutant non-small cell lung cancer patients who are T790 positive. Among a group with no history of CNS metastases, the rate was 10.3 months.
That median PFS rate is down from the 10.4-month PFS rate reported by Clovis last November, which was a distinct disappointment to analysts looking for better numbers to distinguish the therapy from AstraZeneca's AZD9291. Another figure likely to attract unfavorable reviews: The recommended dose in this latest study was 500 mg, down from the 625 mg dose that was ID'd as the go-forward dose last fall. That lower dose may be linked to the lower response rate, which would make Clovis more vulnerable to the competition.
Queried on the lower dose and the lower respone rate, a spokesperson for Clovis noted that the company has been studying a range of doses and that 500 mg was as good and arguably better than the rest, while side effects worsen as you move up on doses.
Regarding the response rate, she added: "In terms of PFS, duration of benefit is very important to patients, but you must understand the characteristics of the patients being treated. To deliver 10.3 months of durability for very advanced patients without brain metastases and 8 months for all T790M positive patients, in which group 40 percent of patients have brain metastases, is phenomenal. It is difficult to make cross-drug or cross-trial comparisons from completely different patient populations, completely different continents and completely different patient characteristics. Clovis' data in a very advanced, mainly U.S. patient population that is representative of the late-stage patients that the academic centers in this country treat is as good as it gets."
The AstraZeneca drug is a top prospect for the pharma giant, which forecast peak sales at $3 billion, and registered a 13.5-month PFS rate just two months ago. The latest AstraZeneca numbers are for EGFR-mutant patients who also had the T790 mutation.
Clovis plans to file roci for approval in about 2 months, looking for a nod later this year. These late-stage moves have kept Clovis in the spotlight among rumored takeover targets in biotech. Bloomberg revived that speculation about 6 weeks ago, the latest in a series of reports over the ast two years that Mahaffy dismisses as "just chatter."
- here's the release on rucaparib
- and the release on roci