Clovis Oncology ($CLVS) is set for an FDA review date of February 23 for lead candidate rucaparib. It’s under priority review as a monotherapy in a tough-to-treat group: ovarian cancer patients with BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations who have been treated with two or more chemotherapies.
The company has now revealed the data upon which its rucaparib NDA is based at the ongoing European Society for Medical Oncology (ESMO) Congress in Copenhagen, Denmark. The FDA has already said that the review process does not require a panel meeting.
Investors were displeased with the data, sending Clovis shares down by more than one-quarter in early trading on the news. The company's shares also plummeted last November when data for the company’s former lead candidate, rociletinib to treat non-small cell lung cancer, had to be restated. Rociletinib eventually endured a negative FDA panel in April, only to subsequently be pulled by Clovis.
The Boulder, CO-based company is now looking to PARP inhibitor rucaparib, the sole clinical asset it has underlying its $1.3 billion valuation. If it’s successful with its FDA review, rucaparib could be the second PARP inhibitor approved by the agency, which first approved AstraZeneca’s Lynparza (olaparib) in December 2014 to treat advanced ovarian cancer associated with defective BRCA genes after it went through a negative FDA panel for maintenance use.
Last month, Tesaro’s ($TSRO) PARP inhibitor niraparib nabbed fast-track designation from the FDA to treat recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. It’s slated to complete a rolling NDA during the fourth quarter; Tesaro is also presenting niraparib data at ESMO. Both Clovis and Tesaro climbed steeply on news of the sale of Medivation, which has its own late-stage PARP inhibitor, to Pfizer ($PFE) for $14 billion.
As for the rucaparib ESMO data, it is based on the combined results of a pair of open-label, single-arm Phase II studies with a 600-mg daily starting dose. The objective response rate among the 106 patients in the efficacy evaluation population was 54%, which included 9 complete responses and 48 partial responses. Another 36 patients had stable disease, while 9 had progressive disease and the remaining four were not evaluable.
Of the 377 patients included in the safety analysis, 8% discontinued therapy due to adverse events, with 44% receiving a reduced dosage due to adverse events. The primary reported patient difficulties were anemia, fatigue and nausea. Nine patients had adverse events that led to death, of which 8 were due to disease progression and one was due to sepsis, which was determined to be unrelated to the treatment.
“These data are very robust,” the study’s lead investigator, Dr. Rebecca Kristeleit, told FierceBiotech. "This is quite a difficult group of patients to treat. Sixty percent have already moved through three prior lines of chemotherapy and a quarter of them were refractory. In that population, getting a response rate at all is extremely clinically important. That gives it the hallmark of a drug you would want to access in this group. The efficacy data are very promising and the safety data are saying that patients can stay on drug for a long time, but they might need to make some adjustments. This drug has some potential in the treatment of ovarian cancer.”
Kristeleit underscored that there is very little monotherapy, rather than post-treatment maintenance, data on PARP inhibitors; she noted that rucaparib is in a pair of Phase III trials, one in ovarian cancer maintenance after chemotherapy and another randomized comparing it as a monotherapy to standard chemotherapy.
The latter is a study of 345 patients with relapsed, BRCA-mutant, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer; the primary endpoint is progression-free survival with an overall survival secondary endpoint. The final primary outcome data is anticipated in 2020.