One key incentive for Pfizer paying $11 billion for Array BioPharma was the positive early readouts from its triplet therapy for colorectal cancer. Now, the biotech has shown exactly how attractive that data are.
A combination of Array’s BRAF inhibitor Braftovi, its MEK inhibitor Mektovi and the anti-EGFR drug Erbitux significantly extended lives of previously-treated patients with certain BRAF-mutant metastatic colorectal cancer (mCRC) to a median of 9 months, versus 5.4 months in those who received Erbitux and chemo.
But the key question for Pfizer’s future sales is whether both Array drugs are needed to reach that kind of result. Would just one do? Analysts are split on that question.
In the phase 3 Beacon trial, the Braftovi and Erbitux duo also extended patients’ lives by 8.4 months. There’s no doubt overall survival came in better for the triple regimen. But a post-hoc analysis on the first half of randomized patients caught analysts’ attention.
Within the first 331 patients, the three-drug combo reduced the risk of death by 26%, delivering a median 9.5 months of life versus the doublet’s 8.3 months—a broader margin than the overall data show. As SVB Leerink analyst Thomas Smith noted, this “more mature subset of data” showed numerical trends that favor the triplet regimen.
But by Evercore ISI analyst Umer Raffat’s rough calculation, it also means the two drug regimens delivered a median OS that was about the same—8.5 months—among the latter half of patients in the trial.
Meanwhile, in all 665 patients, the triplet stalled tumor progression by 4.3 months, while the dual-drug regimen reached 4.2 months.
“[T]he consistency of data in first half of patients (331) versus next half is puzzling … and PFS did not help either,” Raffat said. “In a silo, I’d argue that given the cost differences plus question marks of on incremental efficacy with triplet versus doublet, we may see Pfizer with limited uptake of triplet.”
The side effect rates for the triple combo were higher as well, with 58% of triplet patients suffering Grade 3 or 4 adverse events, compared with 50% among those on the Braftovi-Erbitux doublet, trial investigators said Saturday at the ESMO gastrointestinal conference in Barcelona. Despite that difference, the presentation labeled the triplet’s side effects as “manageable,” and Smith noted that the triplet arm was exposed to the drugs longer than the doublet.
Pfizer is now looking to snatch up Array for a total of $11.4 billion. Before the deal was announced in June, Pfizer had held informal talks with Array about potential team-ups, but it wasn’t until the Big Pharma saw the top-line mCRC data in May that it made its first official offer.
The way Smith sees it, Pfizer has already conducted extensive diligence on the data, and they won’t affect the deal.
Still, as Raffat put it, the $11 billion valuation depends on whether Array will generate $11,000 per month in colorectal cancer—from its own Braftovi alongside Erbitux, which is sold by Eli Lilly—or $23,000 for Braftovi and Mektovi both. He did acknowledge that “in practice, physician experience of using the BRAF-MEK combo in melanoma likely exerts a very positive halo effect” over the colorectal cancer indication.
At least the current trial bodes well for pushing the therapy into earlier lines of use. The response rate for triplet in second line was significantly higher than that in third line, or 34% vs. 14%, Cantor Fitzgerald analyst Varum Kumar noted in a Monday report.
“Assuming the trend holds, we expect Array’s triplet to have a favorable overall profile vs. historical controls in the front line, which is a positive read to the ongoing front-line Anchor colorectal cancer study,” he said. If Braftovi and Mektovi are approved in that condition, Kumar expects the combo could reach $1.1 billion in peak sales.