Merck's 'breakthrough' PD-1 cancer drug in showdown with Bristol-Myers combo

CHICAGO--Jockeying for the lead in the race to win a first approval for a PD-1 cancer immunotherapy, Merck's team arrived at ASCO with some solid positive data backing their melanoma program for lambrolizumab (MK-3475). The pharma giant is readying a pair of late-stage clinical trials for melanoma and non-small cell lung cancer as they set their sights on completing a speedy set of applications for regulators. Those trials launch in the third quarter, but Merck ($MRK) believes that the ongoing Phase II melanoma study with 500 patients could provide enough positive data to win a first approval for a drug designated as a "breakthrough" treatment.

The interim overall response rate for lambrolizumab was 38%, according to investigators, who reported interim data on 135 patients with advanced melanoma. The highest response rate was an impressive 52% in the arm receiving 10 mg/kg every two weeks, the highest dose in the study. Ten percent of the patients in that arm achieved a complete response, with response duration ranging from 28 days to 8 months. Four out of five patients who responded stayed on treatment. And after a median follow-up time of 11 months, the median rate of response has not yet been reached in the study.

The data are good enough to position lambrolizumab as a direct competitor to Bristol-Myers Squibb ($BMY), which has a closely watch PD-1 antibody program of its own for nivolumab. On Saturday, BMS reported that a third of the patients in their Phase I trial saw tumors shrink at least 30%. And they've seen some impressive results after combining their drug with Yervoy, another immunotherapy that relies on a different target. At a high dose, the nivolumab/Yervoy combo produced a 53% response rate, leaving Merck in a head-to-head race. Roche ($RHHBY) is pursuing a PDL-1 therapy that has also garnered the spotlight.

Over the past few years Merck's reputation in drug development has been dominated by a slow and not always steady approach to R&D, with a growing roster of setbacks in the clinic. But there is an air of urgency and excitement around lambrolizumab not often seen at Merck, which spends $8 billion a year on R&D. The first dosing of a patient took place in the fall of 2011, and they had dosed their first patient in a registration study about a year later. Early stage work has been expanded to cover more patients and shoot straight for long-term efficacy data, while the late-stage work is being compressed to speed up planned applications.

"We've never had 1000 patients in a Phase I study before," says Alise Reicin, who heads up the development team for lambrolizumab. And there's no letup in sight. Merck has four clinical studies under way for lambrolizumab in a variety of cancers, with a Phase II under way for melanoma and Phase I trials on Yervoy-naïve patients suffering from triple-negative breast cancer, metastatic bladder cancer and head and neck cancer.

It has helped that Merck won the FDA's breakthrough drug designation, says Reicin, noting that "there's an openness in the dialogue with the FDA that is very positive."  

Executing an efficient drug development program here is a key necessity for Merck, which has been depressing investors with clinical setbacks and a weak slate of Phase III drugs. And now that Roger Perlmutter has returned to Merck to head up R&D, chances are there will be no shortage of support at the top to get the job done here as swiftly as possible. Significantly, Perlmutter himself showed up at the lambrolizumab presentation at ASCO, an indication of his commitment to the program. 

- here's the press release

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