Tesaro ($TSRO) has posted positive top-line results for its experimental PARP inhibitor niraparib for patients who express BRCA--and those who don’t--as it looks to file later this year. Its shares jumped 106% on the news by 10 a.m. ET.
Ben Adams, June 29th, 2016
The Waltham, MA-based biotech said its Phase III trial for niraparib hit its primary endpoint of progression-free survival (PFS) against placebo across several sets of patients--including those who were positive for germline BRCA mutation, and another set that do not carry this mutation--as well as those who have homologous recombination deficient (HRD) tumors as determined by a diagnostic kit.
PFS was met across all 500 patients with the once-daily PARP, with those testing positive for the BRCA mutation seeing a median PFS of 21 months for those on Tesaro’s candidate, compared with 5.5 months for the control group.
In those without the BRCA gene, PFS was 9.3 months vs. 3.9 months in favor of niraparib, with the final subset--those without BRCA mutation but expressing HRD tumors--seeing a PFS of 12.9 months for the drug compared with 3.8 months for the control. No patients died during the study.
Secondary endpoints included overall survival, the golden endpoint in cancer trials--but details of these data have not yet been released.
The biotech is seeking to file for a maintenance indication for ovarian cancer patients in Q4 of this year, according to a statement. Maintenance therapy is for those women who have had prior treatment but are expected to see their cancer return. Its purpose is to avoid or slow a recurrence if the cancer is in complete remission after initial treatment.
Tesaro said that despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, 90% of patients will experience recurrence within two years.
If approved, the biotech said that niraparib may address the difficult “watchful waiting” periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy.
About 22,000 women in the U.S. are diagnosed with a form of ovarian cancer each year.
There are already several personalized meds out there for certain types of ovarian cancer in the form of AstraZeneca’s ($AZN) Lynparza (olaparib)--also a poly ADP-ribose polymerase (PARP) inhibitor--and Roche’s ($RHHBY) blockbuster, multi-licensed Avastin, which gained approval in 2014 for platinum-resistant, recurrent ovarian cancer with chemotherapy.
AZ’s drug has a license for women with heavily pre-treated ovarian cancer that is associated with defective BRCA genes. The drug is expected to make around $2 billion a year at peak.
The FDA based its approval of Astra’s med on a Phase II study comparing Lynparza to a placebo in BRCA-positive patients who'd relapsed after three rounds of chemotherapy.
In the 137-patient study, the drug chalked up a 34% response rate, with half of patients responding for at least 7.9 months. The drug was approved alongside a companion diagnostic, BRACAnalysis CDx, from Myriad Genetics.
Last year, Clovis Oncology ($CLVS) gained a “breakthrough” designation from the FDA for its Pfizer ($PFE)-licensed PARP rucaparib in advanced ovarian cancer in patients who have received at least two lines of prior platinum-containing therapy, with BRCA-mutated tumors, inclusive of both germline BRCA and somatic BRCA mutations.
The drug is expected to be filed with the EMA later this year, with a rolling NDA status ongoing in the U.S. Medivation ($MDVN), the current target of Sanofi ($SNY) and apparently a host of other pharmas, also has its own PARP in the form of talazoparib, which it bought from BioMarin ($BMRN) and is in the latter stages of testing.
PARP inhibitors are designed to zero in on cancer cells and leave a patient's normal cells untouched, although they have not gained the same level of media attention the latest class in oncology, PD-1 and PD-L1 inhibitors, have, with drugs from Merck ($MRK), Bristol-Myers Squibb ($BMY) and most recently Roche all now on the market.
Tesaro is in fact already undertaking studies to combine its drug with Avastin as well as with Merck’s PD1 treatment Keytruda. The combo with Avastin had early data released at ASCO this month, where the company announced the doses had been selected for part two of the trial, although things are still at an early stage.
The company told FierceBiotech that is has “no plans” to conduct any head-to-head trials to compare its drug against either Avastin or Lynparza.
The biotech also signed a deal in April with Johnson & Johnson's ($JNJ) Janssen that sees the Big Pharma’s biotech unit develop and commercialize niraparib for patients with prostate cancer worldwide, except in Japan--but has no rights to its ovarian cancer developments.
The company is also conducting a late-stage trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial), as well as a Phase III in patients with first-line ovarian cancer (the PRIMA trial)--which would move it up the treatment pathway, should it gain approval, and bring in higher rates of revenue. The biotech told me that there is as yet no timeline for the first-line setting, as the trial is only just beginning.
Tesaro originally licensed the drug from Merck back in 2012. Full details of the study are expected to be released later this year.