- The Food and Drug Administration has cleared the AstraZeneca and Merck & Co. drug Lynparza for use in patients with an advanced form of prostate cancer, the second leading cause of cancer death in American men.
- Lynparza is the second so-called PARP inhibitor to win approval for prostate cancer since last week, following the Clovis Oncology drug Rubraca. But Lynparza thus far has shown it can help some prostate cancer patients live longer, which could make it the preferred option of the two. Just 31% of patients whose prostate cancer has spread through the body live a median of five years after diagnosis, despite the availability of many treatments.
- The approvals restrict use of PARP inhibitors to a subset of prostate cancer patients who have failed at least one treatment. But that could change, as Lynparza is being tested alongside hormone therapy in newly diagnosed patients.
Clovis Oncology's moment didn't last very long.
On Friday, the FDA approved Rubraca for use in a genetic subset of advanced prostate cancer patients who had failed at least two treatments. That nod was a milestone: Rubraca became the first member of a relatively new class of drugs called PARP inhibitors, already approved for tumors of the ovary, breast and pancreas, to break into prostate cancer.
The drugs, which block an enzyme tumors use to fix their DNA, are showing an ability to beat standard hormone therapy in some settings, and extend lives as well. Ongoing studies from Clovis, GlaxoSmithKline and AstraZeneca could help their roles could grow.
After Rubraca's approval, Clovis — like many other biotechs on Monday — quickly turned around and raised cash.
But no sooner had Clovis's $89 million share sale closed than the FDA cleared Rubraca's rival, Lynparza, with what analysts believe to be a better-than-expected label that surpasses what the FDA has granted for Clovis' drug.
Rubraca was given a conditional, faster-than-normal approval for third-line use in prostate cancer patients with a BRCA mutation, a subset of about 12% of those with the disease. The approval was based on the results from a small, single arm study in which 44% of patients responded to treatment. Clovis has to confirm the results with additional testing.
Lynparza, by comparison, was granted full approval for second-line use, after hormone therapy, in the 20% to 30% of prostate cancer patients whose tumors have homologous recombination repair mutations — a group that also includes those whose tumors are BRCA-positive. The nod was based on a Phase 3 study in which Lynparza kept these patients' tumors from spreading for a median of 7.4 months, compared to 3.6 months for hormone therapies like Xtandi and Zytiga — the first such result for a PARP inhibitor in a Phase 3 trial in prostate cancer.
And Lynparza's prescribing information includes the recent disclosure that the drug helped extend patients' lives compared to hormone therapy in a Phase 3 trial. The drug cut the risk of death by 31% compared to standard treatment — patients lived an additional 19 months, compared to 14.6 months for those on hormone therapy. It wasn't clear whether the FDA would put that data in Lynparza's initial label, given the results came in late April.
The approval comes with "a significantly better label than we anticipated," wrote SVB Leerink analyst Andrew Berens. The broad label, earlier line usage, and survival benefit seen thus far "will rapidly establish Lynparza as the drug of choice in the 2nd line, leaving little commercial opportunities for Rubraca downstream in the 3rd line," Berens added in a note to investors.
Lynparza already paces the PARP field, with $1.2 billion in sales in 2019. Rubraca, by comparison, generated $143 million.
Clovis could run into additional competition too. Zejula, a PARP drug to which Johnson & Johnson holds rights in prostate cancer, produced Phase 2 results in the disease last year. The FDA granted a Breakthrough Therapy designation to Zejula, which should speed up its review. And Lynparza is being tested alongside hormone therapy in newly diagnosed prostate cancer patients.
Clovis shares fell 16%, to $7.52 apiece, on Tuesday, a day after its share sale. Berens believes the company may need to raise another $275 million next year to stay afloat and cover the roughly $64.4 million in convertible debt that comes due in September 2021.