Results

Merck halts enrollment on two PhIII Keytruda combo studies as outside monitors flag a worrying rate of deaths

Merck $MRK has had to hit the brakes on enrolling new patients for two of its late-stage combo studies involving its blockbuster checkpoint Keytruda after the monitoring committee raised a red flag on an imbalance of deaths in the studies involving multiple myeloma.

Treatment in the two trials will continue, says Merck, as they try to evaluate why there were more deaths in the Keytruda arms of KEYNOTE-183 and KEYNOTE-185. The trials involve combinations with Celgene’s Pomalyst as well as its flagship drug Revlimid in a field Celgene dominates in.

Merck shares slid 1.3% as investors got their first whiff of bad news about Keytruda in some time.

Roger Perlmutter, Merck

Keytruda isn’t just Merck’s biggest drug in the pipeline. It represents a pipeline of its own for R&D chief Roger Perlmutter, with dozens of combination studies underway as the pharma giant hurries to expand its use. These checkpoints, including Bristol-Myers Squibb’s Opdivo, have had a major impact for some patients, unleashing an immune system attack on cancer cells in a variety of tumors. But their growing use has come with a number of nasty surprises over what works and what doesn’t, as Roche found when its PD-L1 superstar Tecentriq failed a recent Phase III.

Right now, though, there’s no exact explanation for what triggered the imbalance in deaths among a very sick group of patients who had already failed earlier therapies.

Explains Merck:

KEYNOTE-183 is a Phase 3 study comparing pomalidomide and low-dose dexamethasone with KEYTRUDA to pomalidomide (Pomalyst) and low-dose dexamethasone alone in patients with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treatment. KEYNOTE-185 is a Phase 3 study comparing lenalidomide (Revlimid) and low-dose dexamethasone with KEYTRUDA to lenalidomide and low-dose dexamethasone alone in patients with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT).

Credit Suisse analysts were ready to shrug off the jitters. In a note, they reported:

We spoke with MRK, and they confirmed that this is not a clinical hold; enrolled patients are continuing with their treatment regimens. However, they were not able to provide additional color regarding how many patients have died, or whether the imbalance was seen in both studies, or just one study with both halted for precautionary measures. We have seen data from the Pomalyst combo before in a Phase I study that was presented at ASH in 2015, and there were no signs of an obvious toxicity with the combination that were of concern to doctors.


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RAPS Regulatory Convergence 2017