BARCELONA—Quietly, and without the fanfare of gene and cell therapies, PARP inhibitors from the likes of AstraZeneca, Merck and GlaxoSmithKline's Tesaro have been racking up big trial wins in breast, ovarian and other cancers.
These wins have helped spur the revitalization of AZ’s cancer prospects and the buyout of Tesaro via GSK, all the while boosting survival in some difficult-to-treat tumors. But it’s not been a complete success story, with AbbVie, already bringing up the rear with veliparib, being beset by a series of flops with its PARP drug in recent years.
Trouble started back in 2016, when AbbVie missed its survival targets in a midstage trial of its PARP inhibitor in breast cancer when combined with chemo, failing to significantly delay the time to cancer progression or extend lives.
Here, its drug, a poly (ADP-ribose) polymerase (PARP) inhibitor, which is designed to stop cancer cells being able to repair, was being tested among patients who had locally recurrent or metastatic breast cancer with BRCA1 or BRCA2 mutations.
The biopharma was down but not out, it said at the time, looking to later-stage efforts in different settings for reprieve. These came in the shape of two phase 3 tests in 2017, but the data showed no reprieve: Veliparib plus chemo again missed its primary endpoints, failing to improve outcomes in patients with non-small cell lung cancer (NSCLC) or triple negative breast cancer.
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At the European Society for Medical Oncology (ESMO) annual meeting this weekend in Spain, however, AbbVie finally got a phase 3 win with veliparib alongside two chemo regimens, as this cocktail managed to hit its primary endpoint in keeping cancer from worsening.
Breaking it down, the so-called Velia trial tested the drug in patients with newly diagnosed late-stage epithelial ovarian, fallopian tube or primary peritoneal cancers.
Three populations were studied, including two biomarker-selected patient populations and without a biomarker. In all patient populations, median progression-free survival (PFS) “was higher for those receiving carboplatin and paclitaxel (CP) plus veliparib with single agent veliparib, versus patients receiving CP plus placebo with placebo,” the company told FierceBiotech.
The PFS for the veliparib with chemo and as a single agent group was 34.7 months and 31.9 months BRCA-mutated and in the homologous recombination deficiency populations, respectively, and 23.5 months in the entire population, compared to 22 months, 20.5 months and 17.3 months, respectively.
The ovarian cancer data were published Saturday; Sunday, it released data out of its BROCADE3 phase 3 test, which looked at veliparib in combo with chemo agents carboplatin and paclitaxel in BRCA mutated, triple negative or hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer.
It managed to get a hit here, too, in PFS when compared to the placebo combo, but only by about two months: Median investigator assessed PFS in patients getting the veliparib combination was 14.5 months, compared to 12.6 months in the placebo combination. Statistically significant, but not earth-shattering.
The veliparib-plus-chemo cocktail did also see durable benefit, with just over a quarter of patients living progression-free at three years, compared to 11% in the placebo group.
AbbVie notes that this is “the first phase 3 study of a PARP inhibitor to demonstrate improved PFS when combined with a highly active platinum-based chemotherapy regimen compared to chemotherapy alone.”
But, as with its ovarian data, these breast cancer results still leave AbbVie in a quandary as to how and where it could fit into a highly competitive and now long-standing market.
While undoubtedly these studies are a win and much needed in terms of previous failures, just how marketable this drug can be in competition with GSK's Zejula and AstraZeneca and Merck's Lynparza remains to be seen, and it being such a problem child over the past three years does little to add to its appeal.
After its last 2017 failure, analysts at Jefferies said as much, noting that the PARP inhibitor accounted for less than 1% of their midterm revenue forecasts. That modeling makes veliparib a small piece of the late-phase blitz AbbVie has embarked on to equip its business to weather the impact of biosimilar competition for its cornerstone drug Humira.
And AbbVie itself told FierceBiotech that it is only “continuing to analyze the data and will be working with regulatory agencies worldwide to explore the potential of bringing veliparib to patients in need" and not confirming that it absolutely will be filing the drug.
Its bigger prospect was lung cancer hopeful Rova-T, bought out in a near $6 billion deal from biotech Stemcentrx, but calamity struck this drug and this deal, with a strong of flops leading to it being officially tossed out last month.