AstraZeneca, Merck herald PhIII prostate cancer win for Lynparza — overtaking Clovis, J&J in PARP race
The case for expanding Lynparza’s use just got stronger as AstraZeneca and Merck claim a late-stage success in extending the time prostate cancer patients live without progressing compared to standard of care.
Rivals at Clovis provided the first resounding evidence that PARP inhibitors could be powerful against metastatic castration-resistant prostate cancer last October, when it unveiled at ESMO that Rubraca induced a 44% confirmed objective response rate among 25 second-line patients with a BRCA alteration. Days prior to the presentation, the Phase II data had earned the biotech a “breakthrough” designation at the FDA.
AstraZeneca and Merck took it a step further with their Phase III results, touting “a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS).” No numbers were available with the top-line announcement, but the pharma partners emphasize it’s a first in the PARP class for this indication, where the need is high.
“For men with metastatic castration-resistant prostate cancer the disease remains deadly, especially in those who have failed on a new hormonal anticancer treatment,” José Baselga, AstraZeneca’s head of oncology R&D.
The 340 patients recruited in the PROfound study are all confirmed, via genomic testing to harbor mutations in one of 15 homologous recombination repair genes. They have also all progressed following prior treatment with hormonal therapy.
In the open-label trial, patients were either given Lynparza, enzalutamide or abiraterone acetate.
In their analysis investigators zeroed in on BRCA1/2 — a key qualifier for previous wins in ovarian, breast and pancreatic cancers — and ATM gene mutations. The effects of Lynparza, which blocks a self-repair mechanism adopted by cancer cells, on the other patient subgroups remain unclear.
AstraZeneca reported Lynparza sales of $520 million in H1 2019, far ahead of the $66.1 million Clovis’ Rubraca managed to garner in the same period. Zejula sales were around $120 million, and J&J (which licensed rights to the prostate cancer indication from Tesaro back in 2016) has demonstrated a 40% ORR in a Phase II study for the GlaxoSmithKline drug. Clovis plans to submit an NDA in the fourth quarter of this year.
Meanwhile, Merck has kicked off an umbrella study pairing its PD-1 star Keytruda with a number of other agents, including Lynparza, for prostate cancer, with an ambition to move to the frontline.