Tesaro, Inc. (NASDAQ: TSRO) markets a highly successful therapy for ovarian cancer, Zejula, and its plans for the future include winning approval of Zejula's use alongside another one of its drugs, TSR-042, in non-small cell lung cancer. Will this combination therapy reshape how oncologists treat lung cancer?
A one-two punch
Zejula is a poly ADP-ribose polymerase (PARP) inhibitor that helps prevent PARP enzymes from repairing damaged cancer cells. Unable to rely upon the body's natural cell repair system, cancer cells stand less of a chance at survival.
Initially, Zejula's trials focused on late-line ovarian cancer patients with BRCA mutations. Normally, BRCA helps repair double-strand DNA breaks, but in patients with BRCA mutations, BRCA doesn't work properly, so the heavy lifting of cell repair is done by PARP. The use of PARP inhibitors in BRCA-positive patients is effective because it results in the disruption of both repair mechanisms; however, Zejula also works in non-BRCA mutant cancer patients, suggesting its efficacy is also due to PARP's role in supporting immune system function.
Tesaro secured an FDA OK to market Zejula as a once-daily maintenance therapy for use in patients who've responded to platinum-based chemotherapy, regardless of BRCA status, in March 2017.
Zejula's ability to delay disease progression following chemotherapy has made it one of the fastest-growing cancer drugs. In Q2, its sales were $54 million, up 108% from the year prior. The drug's market opportunity might not be limited to ovarian cancer, either. Increasingly, researchers think PARP inhibition can be used to improve the efficacy of PD-1 inhibitors, a class of drugs that are increasingly being used in lung cancer.
T-cells are one of the body's most important weapons in the fight against disease. One way T-cells determine which cells to attack is by whether or not their PD-1 checkpoint receptor has been activated or inactivated. It the PD-1 checkpoint binds to a PD-L1 protein expressed on a cell, then it leaves that cell alone and moves on to the next cell. Unfortunately, some cancers hijack this mechanism, in effect rendering them invisible to T-cells.
Over the past few years, a number of PD-1 inhibitors have won FDA approval, but the two top-sellers in this class of drugs are Opdivo and Keytruda. Both of those drugs owe a good deal of their commercial success to their uses in lung cancer. In Q2, Opdivo's sales were $1.63 billion, and Keytruda's sales were $1.67 billion, giving each an annualized sales run rate in excess of $6.4 billion.
PD-1 inhibitors success has resulted in various companies, including Tesaro, developing their own PD-1 drugs so they can build combination therapies that they own entirely. In Tesaro's case, its PD-1 inhibitor, TSR-042, is being evaluated for use alongside Zejula in platinum-resistant refractory ovarian cancer and non-small lung cancer. It's also under investigation as a monotherapy for lung cancer and MSI-high-expressing endometrial tumors.
In non-small cell lung cancer, the combination study is in phase 2 as a first-line treatment. During the company's second-quarter conference call, management said it's pleased with the data so far, and that results will be presented at an industry conference in the first half of 2019. The monotherapy study of TSR-042 is for second-line non-small cell lung cancer patients whose disease has progressed following chemotherapy. Management says data so far is "competitive with data from marketed anti-PD-1 antibodies in the second-line setting."
On Wednesday, Tesaro offered investors more insight into the progress it's making with its combination study. Specifically, after 100% of the 14 patients participating in the first stage experienced tumor shrinkage, and 64% of them had an objective response, Tesaro decided to advance TSR-042 plus Zejula into a second stage that will enroll 36 more patients.
What to watch next
Over 150,000 Americans die because of lung cancer every year, so there's a significant need for new lung cancer treatment alternatives. Tesaro hasn't licensed TSR-042 or Zejula, so this two-pronged approach could become a wholly owned blockbuster if studies pan out.
Next year, investors will want to keep an eye out for updates on the combination study, but data from the trial evaluating TSR-042 as a monotherapy could also be market-moving. Tesaro intends to begin a registration enabling phase 2 trial of TSR-042 versus standard of care in the first-line lung cancer setting in early 2019.