- Treatment with AstraZeneca's Lynparza (olaparib) reduced the risk of disease worsening or death by 42% in patients with a mutated form of metastatic breast cancer, the first positive Phase 3 results of a PARP inhibitor outside of the ovarian cancer setting.
- Lynparza, the cornerstone of the British pharma's efforts in DNA damage response, delayed progression by roughly three months compared to an investigator's choice of three types of chemotherapy. AstraZeneca had previously said the trial, known as OlympiAD, met its primary endpoint but hadn't disclosed any specifics.
- PARP inhibitors block a certain type of DNA repair, counter intuitively exploiting an underlying defect in cancer cells with germline BRCA mutations to trigger cell death. Two other drugs, Clovis Oncology's Rubraca (rucaparib) and Tesaro's Zejula (niraparib) have recently secured approval in ovarian cancer, giving Lynparza new competition in that indication.
Lynparza is a key drug in AstraZeneca's push to establish a "new oncology" growth platform, and succeeding outside of ovarian cancer will help build on its existing competitive advantage just as new rivals come onto the market.
"[The OlympiAD result] also lends a lot of credence to some of the other areas in which we are exploring down the road as well with Lynparza in other tumor types — prostate cancer, pancreatic cancer, etc.," said Michelle Werner, VP of U.S. Oncology at AstraZeneca, in an interview.
OlympiAD read out results from 302 patients with HER2-negative, BRCA-mutated metastatic breast cancer who were administered Lynparza as either first-, second- or third-line of treatment. About 60% of patients saw their tumors shrink, a hair more than double the 29% objective response rate seen in those patients on chemotherapy.
Lynparza showed efficacy in patients with a type of breast cancer known as triple negative, which is considered more difficult to treat. AbbVie, which is developing its own PARP inhibitor called veliparib, recently announced a study specifically geared to look at veliparib's activity in triple negative breast cancer failed to show a benefit when added to chemo.
Additionally, treatment with Lynparza improved the time to second progression or death compared to chemo, suggesting patients who relapsed after Lynparza experienced a less aggressive return of their cancers.
No overall survival results were presented, however, and it's not yet clear which breast cancer patients would respond the best to Lynparza, notes a statement on the data from American Society of Clinical Oncology.
Sales of Lynparza totaled $57 million over the first three months of 2017, but U.S. revenues declined slightly compared to the same period a year ago.
"We have seen competitive pressure in marketplace in the U.S., and that's due to early entry of competitors," Jamie Freedman, head of oncology, said on an April 27 call with analysts.
"But we're optimistic because we've had positive news," he explained at the time, noting the positive SOLO-2 and OlympiAD results. "Overall, we do expect an uptick in sales, particularly in the third quarter, and then at the end of the year."
Strong results announced in March from a confirmatory study in ovarian cancer patients demonstrated Lynparza cut the risk of disease progression by 70% compared to placebo — data that should help move treatment with the drug earlier and support sales growth.
Continued success with Lynparza also helps underpin AstraZeneca's strategy of pursuing combinations, Werner said. The pharma hopes to find efficacy in pairings across its cancer portfolio, headlined by its checkpoint inhibitor Imfinzi (durvalumab) but also including Lynparza and other DNA damage response agents.
A combination of Imfinzi with an experimental immunotherapy called tremelimumab has been closely followed as it's thought to be AstraZeneca's main chance to gain ground on competitors in immuno-oncology.