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Merck and AZ pile on more positive Lynparza data in bid to break into prostate cancer

Lynparza bottle
Lynparza beat analysts’ expectations in the second quarter with $283 million in sales. (AstraZeneca)

Two months back, AstraZeneca and Merck made a strong case at the American Society of Clinical Oncology (ASCO) annual meeting that Lynparza should be the first PARP inhibitor approved to treat prostate cancer, with data showing the drug significantly delayed disease progression when added to Johnson & Johnson’s Zytiga.

Now the Lynparza partners have a fresh set of data to back up their case, and this time it’s for use of the drug as a solo therapy.

Merck and AstraZeneca said they have seen positive results from a phase 3 trial of Lynparza in men with metastatic castration-resistant prostate cancer and a mutation in a homologous recombination repair (HHR) gene. The men in the trial had progressed after receiving either Zytiga or Astellas’ and Pfizer’s Xtandi.

The companies said there was a “statistically significant and clinically meaningful improvement” in progression-free survival among trial participants taking Lynparza over those on either Zytiga or Xtandi. They plan to present the full data at an upcoming medical meeting.

It’s the latest twist in what has become a mad race to the finish line for PARP inhibitors in prostate cancer. Lynparza was already locked in a battle for market share with Tesaro’s Zejula and Clovis’ Rubraca in ovarian cancer. Then AstraZeneca and Merck pulled ahead of their rivals last year when the FDA approved Lynparza for the treatment of BRCA-mutated breast cancer. But Tesaro, now owned by GlaxoSmithKline, and Clovis are testing their PARP inhibitors in breast and prostate cancer, too.

BRCA1 and BRCA2 are two of 15 genes in the HRR pathway that can be mutated in prostate tumors, and AstraZeneca and Merck have set out to prove that Lynparza can offer a targeted treatment option for patients with those gene abnormalities whose disease has progressed. In addition to studying the drug as a monotherapy, the companies are trying it in combination with Merck’s blockbuster immuno-oncology drug Keytruda in patients with metastatic castration-resistant prostate cancer.

That’s one of three new phase 3 trials of Keytruda in prostate cancer that Merck unveiled earlier this year. Merck is also trying Keytruda with docetaxel and prednisone, and with Xtandi. That announcement came just after Merck released data from its Keynote-365 trial showing that all three combos produced significant decreases in prostate-specific antigen (PSA), the protein that’s commonly elevated in men with prostate cancer. In the Lynparza-Keytruda trial, 12% of prostate cancer patients saw PSA declines of 50% or more.

Still, Zejula and Rubraca can’t be counted out of the prostate cancer race by any stretch. Last October, Clovis nabbed a breakthrough designation for Rubraca in prostate cancer based on data from a trial showing that 44% of patients with BRCA 1/2 mutations responded well to the drug. J&J’s Janssen, which is developing Zejula in prostate cancer, announced in February that in a phase 2 trial, the drug produced a 40% response rate among prostate cancer patients with BRCA 1/2 mutations.

In fact, when GSK announced its $5.1 billion purchase of Zejula maker Tesaro late last year, its executives cited the drug’s potential to succeed in markets beyond ovarian cancer as a key factor in its decision to pay a 62% premium for the biotech.

No doubt investors will be watching AstraZeneca and Merck’s prostate cancer results carefully has they handicap the chances for all of the contenders in the PARP race. José Baselga, executive vice president of R&D for AstraZeneca, said in a statement that the results announced Wednesday for Lynparza in mutated prostate cancer mark “the only positive Phase III trial of any PARP inhibitor” in that patient population. “We look forward to discussing these results with global health authorities soon,” he added.