BioMarin Pharmaceutical received $20 million in milestone payments from Pfizer after the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved its applications for talazoparib.
BioMarin Pharmaceutical received $20 million in milestone payments from Pfizer after the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved its applications for talazoparib.
Talazoparib is a once-daily, oral poly ADP ribose polymerase (PARP) inhibitor being evaluated in clinical trials for patients with germline BRCA 1 and 2-mutated locally advanced or metastatic breast cancer.
These were part of a deal made when Pfizer acquired Medivation. In August 2015, Medivatiorn and BioMarin inked an asset purchase deal where Medivation bought all the worldwide rights to talazoparib for use in breast cancer treatment. Under that deal, Medivation, subsequently acquired by Pfizer, is responsible for all research, development, regulatory and commercialization activities for all indications.
Under the original deal, Medivation paid BioMarin $410 million upfront. BioMarin is eligible for up to another $160 million in total payments based on various regulatory and sales-based milestones. It is also eligible for single-digit royalties.
The FDA accepted the filing today and granted it Priority Review, which triggered part of the milestone payment. The EMA’s acceptance of the Marketing Authorization Application (MAA) triggered another part.
“Women with hereditary BRCA mutation are typically diagnosed with breast cancer at a younger age than the overall breast cancer population and have limited treatment options when they develop advanced disease,” said Mace Rothenberg, Pfizer Global Product’s chief development officer, in a statement. “Today’s filing acceptances are just the latest example of the success of Pfizer’s precision medicine approach to drug development, in this case targeting the faulty DNA damage repair process associated with BRZCA mutations. We are now one step closer to offering a potential alternative to chemotherapy for these patients.”
The PDUFA date by the FDA is in December 2018.
The data supporting the submissions came from the EMBRACA Phase III clinical trial, which evaluated talazoparib compared to physician’s choice chemotherapy (capecitibine, eribulin, gemcitabine or vinorelbine) in 431 patients. The patients had an inherited BRC1/2 mutation and locally advanced or metastatic triple negative or home receptor-positive (HR+)/HER2- breast cancer. The trial’s primary endpoint, which was met, was superior progression-free survival (PFS) with the drug compared to chemotherapy.
The study indicated a 45.8 percent decrease in the risk of disease progression for patients on the drug. Median PFS was 8.6 months compared to 5.6 months in the control group. Although not necessarily comparable from different studies, competitor AstraZeneca and Merck’s Lynparza (olaparib) had a 42 percent decrease in the risk of progression, with a PFS of 7 months compared to 4.2 months.
There are already three PARP inhibitors on the market. They are Clovis’ Rubraca, Tesaro’s Zejula and AstraZeneca and Merck & Co’s Lynparza. Lynparza was the first in the class to be approved in breast cancer in January.
When Medivation was being acquired by Pfizer, then-chief executive officer David Hung indicated talazoparib was going to be best-in-class, and told analysts it was a “multibillion-dollar opportunity.” Which at least partly explains why Pfizer coughed up $14 billion for the company, a price tag many industry analysts felt was too high. Although the data is probably good enough to gain approval, it may not necessarily be good enough to beat off Lynparza and make back the money the company invested in it.
Researchers from the Institute of Cancer Research in London published research in Nature Communications in May that helped to identify why some people are resistant to PARP inhibitors. They used CRISPR gene editing to help identify DNA mutations in the PARP1 gene that lend immunity against PARP inhibitors.
The study’s lead author, Stephen Pettitt, told Forbes, “Testing for the mutations we have identified could offer even more personalized treatment for women with breast and ovarian cancer, by following doctors to judge whether and for how long olaparib should be used.”
