- The Food and Drug Administration on Wednesday approved AstraZeneca and Merck & Co.’s Lynparza for use in certain people newly diagnosed with advanced prostate cancer.
- Lynparza is already available in the U.S. for prostate cancer patients whose disease has progressed following treatment with one of two commonly-used therapies. The new approval covers earlier use, alongside one of those treatments — Zytiga — and a steroid.
- Still, treatment isn’t cleared for prostate cancer broadly, as the developers had originally hoped. The FDA limited its approval to only prostate cancer patients with BRCA mutations, a group that accounted for about 11% of participants in the study supporting Lynparza’s approval. The benefit reported in that trial was “primarily attributable” to patients with BRCA mutations, the regulator said in a statement.
Lynparza’s narrow label in front-line prostate cancer reflects a “shift in the regulatory and clinical perception” of the drug and others like it, collectively known as PARP inhibitors, wrote SVB Securities analyst Andrew Berens in a Wednesday note.
Several PARP inhibitors are available to treat ovarian, breast, pancreatic and prostate tumors. They’re typically used as “maintenance” therapies — meant to slow cancer’s return after a tumor is surgically removed or eliminated by other drugs. In recent years, they have shown potential in earlier lines of care, too.
Yet the view of PARP drugs has changed in the last year. Studies have shown the drugs don’t help certain ovarian cancer patients live longer and, in some cases, may increase their risk of death. Those findings led to market withdrawals by AstraZeneca and Merck, GSK and Clovis Oncology in certain ovarian cancer indications in the U.S.
The data supporting AstraZeneca and Merck’s latest application also drew scrutiny from the FDA, which deferred a decision last year and scheduled an advisory committee meeting in April to scrutinize the data.
The partners had reported the Lynparza-based regimen held tumors in check a median of eight months longer than a combination of hormone therapy and steroids, regardless of patients’ underlying genetics. They also cited a numerical, but not statistically significant, survival benefit.
However, FDA scientists and most panelists at the meeting agreed the results were driven by the 11%, or 85, of study volunteers with BRCA mutations. In slides presented at the meeting, FDA reviewers noted “modest efficacy” and “potential harm” in the much larger group of patients without those mutations. Panelists voted 11-1, with one abstention, to recommend restricting use to the smaller group.
Analysts are lowering sales forecasts as a result. Berens, for instance, once modeled up to $4.2 billion in potential peak sales in the U.S. and Europe for Lynparza in prostate cancer. He cut his projection to $1.2 billion after the meeting. And on Wednesday, Berens estimated $680 million in yearly sales potential in the U.S. (The drug has a broader label in Europe, where regulators have taken a different view of the Lynparza results.)
The FDA’s decision could have implications for Pfizer, which in February reported positive Phase 3 results for its PARP blocker Talzenna in front-line prostate cancer. Pfizer said it saw a benefit regardless of patients’ genetics. However, it was too early to tell whether Talzenna helped patients live longer.