Clovis Oncology's (CLVS +0.00%) Rubraca is already approved for use in ovarian cancer patients who have seen their disease return following two or more chemotherapies. Soon, the Food and Drug Administration may clear its use in patients following one or more treatments.
Improving outcomes in ovarian cancer
Rubracra inhibits poly (ADP-ribose) polymerase, or PARP, proteins associated with DNA repair, genomic stability, and programmed cell death.
IMAGE SOURCE: GETTY IMAGES.
Usually, PARP's activity is a good thing. But in ovarian cancer patients, PARP can repair cancer cells, boosting their survival and proliferation.
Fortunately, new drugs that inhibit PARP's activity have become available. They can delay disease progression in patients who have seen their disease return following chemotherapy.
In 2014, the FDA approved AstraZeneca's (AZN +0.00%) PARP inhibitor, Lynparza, for use in patients who have received three or more chemotherapies, and who tested positive for BRCA gene mutation. In trials, Lynparza delivered an objective response rate (complete response or partial response) of 34%.
Then came the December 2016 FDA approval of Clovis Oncology's Rubraca for use in BRCA-positive patients following two or more chemotherapies. In trials, the objective response rate to Rubraca was 54%.
Most recently, Tesaro's (NASDAQ: TSRO) PARP inhibitor Zejula won approval in March 2017 as maintenance therapy for ovarian cancer patients who have received one or more chemotherapies, regardless of BRCA status. That approval was based on Zejula producing progression-free survival of 21 months versus 5.5 months for the placebo arm in BRCA-positive patients, and progression-free survival of 9.3 months versus 3.9 months for the control arm in non-BRCA-positive patients.
Earlier and earlier use
Zejula's approval as maintenance therapy across all ovarian cancer patients cleared the way for doctors to use PARP inhibitors earlier in treatment, but that advantage could be short-lived.
In March, AstraZeneca reported data showing that Lynparza is effective in the one-or-more-chemotherapies setting, and today, Clovis Oncology reported results showing Rubraca is effective in that setting too.
In the case of Clovis Oncology, today's report shows that use of Rubraca maintenance therapy led to progression-free survival of 10.8 months in the intent-to-treat population, versus 5.4 months for placebo. In BRCA-positive patients, the progression-free survival in this trial was 16.6 months, versus 5.4 months for placebo.
Clovis Oncology also said today that some patients who enrolled in its trial with residual disease saw their tumor burden shrink on Rubraca maintenance therapy, and that Rubraca's safety was in line with what's been observed previously.
The company plans to use this data to file for approval of Rubraca as a maintenance therapy in patients following one or more chemotherapies within four months; the drug could win an official FDA green light for use in these patients in the first half of 2018. A decision on Lynparza in this setting is expected in the third quarter of 2017.
More data on deck
Competition among PARP inhibitors is fierce: Strong efficacy across this class of drugs suggests that all three names could win approvals for front-line maintenance use.
AstraZeneca is expected to report results from a front-line maintenance trial for Lynparza this year, and if that trial pans out, a filing for approval in that setting could happen in early 2018. Similarly, Tesaro is enrolling patients in a first-line trial, and Clovis Oncology (not to be left out!) is evaluating Rubraca in the first-line setting as well.
Because data in the first-line setting is still coming, the PARP battle between these three companies is far from over.
