Tesaro, Inc. (NASDAQ: TSRO), Clovis Oncology (CLVS -7.00%), and AstraZeneca PLC (AZN 0.97%) all sell ovarian cancer drugs that work similarly, and the three companies are locking horns in a battle for market share.
This week, Tesaro unveiled data from a study of its drug, Zejula, that might give it an edge. Let's take a closer look.
First, let's set the stage
All three of these drugs have the same mechanism of action: They inhibit poly (ADP-ribose) polymerase (PARP), an enzyme that repairs damaged cells. In healthy patients, PARP plays a valuable role; however, in cancer patients, it can keep damaged cancer cells from dying.
In 2014, AstraZeneca launched the first PARP inhibitor, Lynparza, after it was proven effective in ovarian cancer patients who had BRCA gene mutations and had received at least three prior chemotherapies. Like PARP, BRCA genes repair cell damage; however, mutations in those BRCA genes can contribute to the development of certain cancers, including ovarian cancer and breast cancer.
Lynparza's label has since been expanded to include its use as a maintenance therapy in patients who are in complete or partial response to chemotherapy, regardless of their BRCA status. In January, Lynparza also won approval from the Food and Drug Administration for use in BRCA-positive, metastatic breast cancer.
Lynparza had a head start, but competitors began to catch up quickly last year. In December 2016, Clovis Oncology secured FDA approval of Rubraca as the first PARP treatment for use after two prior chemotherapies. In March 2017, Tesaro's Zejula won FDA approval as a maintenance therapy for ovarian cancer, regardless of BRCA status.
A new discovery
In a bid to differentiate Zejula from Lynparza and Rubraca, Tesaro is investigating its use alongside PD-1 checkpoint inhibitors, which are widely used to treat many cancers. Based on the data reported on Tuesday, it appears Tesaro is onto something.
In a phase 1 and 2 study evaluating the addition of Zejula to the multibillion-dollar PD-1 inhibitor Keytruda, 25% of patients who were resistant or refractory to platinum-containing chemotherapy had a complete or partial response that wasn't dependent on BRCA status. When patients who achieved stable disease were included, the disease control rate for this combination therapy was 68%.
Those rates are pretty good, especially compared to what's been observed in this patient population in the past. Typically, the overall response rate in platinum-resistant ovarian cancers treated with standard-of-care chemotherapy ranges between 5% and 18%. The response rate is even lower for refractory patients.
The data also suggests there's a benefit from using these drugs together. For perspective, response rates to PD-1 drugs in this patient population have capped out at 15%, and they've only been between 5% and 10% when PARP has been used as a monotherapy.
No winner yet
This data will need to be confirmed, but Tesaro is planning a study that will pair up Zejula with a PD-1 inhibitor that it's developing on its own. If that study succeeds, Tesaro could wind up with a wholly owned combination therapy that could be used in about 10,000 tough-to-treat patients each year in the U.S. alone.
Nevertheless, this is only one indication that these PARPs are being studied in, and Clovis Oncology and AstraZeneca are hard at work conducting their own trials. The FDA may allow expansion of Clovis Oncology's Rubraca into the maintenance setting in April, and studies are underway that are evaluating Rubraca alongside PD-1 drugs. At AstraZeneca, Lynparza could get filed for approval as a first-line ovarian cancer treatment this year, and a filing could come as soon as next year in pancreatic cancer if trial results cooperate.
Clearly, the PARP battle for market share is far from over, and that makes keeping tabs on these stocks important.