Cancer immunotherapy is, in a word, tantalizing. It might save the life of someone at death’s door and keep the cancer at bay for years. Or it might not work at all. There’s no telling what a patient will experience.
“There’s a real poverty of understanding of how the machine that is us works,” says Roger Perlmutter, the executive vice president of pharmaceutical giant Merck (NYSE: [[ticker:MRK]]) and the head of its research division, Merck Research Laboratories.
Perlmutter (pictured) lives this dilemma. He and his team shape Merck’s immunotherapy strategy and its sprawling network of trials, and pick which drugs to pair with the company’s flagship pembrolizumab (Keytruda). More than half of the 900 or so ongoing trials involving pembrolizumab combine the Merck drug with another treatment.
Since he left Amgen (NASDAQ: [[ticker:AMGN]]) to return to Merck in 2013, Perlmutter has seen pembrolizumab come to market and become the most lucrative cancer immunotherapy in the world. It is on track to generate more than $6 billion in sales in 2018, thanks to approvals in 10 different types of cancer, and has surpassed a rival drug from Bristol-Myers Squibb (NYSE: [[ticker:BMY]]) to become the standard of care, alongside chemotherapy, for a majority of people with advanced lung cancer. “The impact that it’s having on patients with advanced malignant diseases is remarkable,” Perlmutter says.
But Perlmutter is dealing with the same problem as the biopharma industry writ large. Immunotherapy, for all of its promise, works for only 20 to 30 percent of patients whose immune systems are revved up enough to wipe out their cancers. Merck is racing Bristol, Roche/Genentech, and others to learn why most patients don’t respond, and to boost their results by pairing the right drugs and technologies with immunotherapies like pembrolizumab.
The race has had its share of critics. In interviews with Xconomy, many oncologists have chided companies for moving too fast, running redundant studies, and launching trials of combination therapies with inadequate grasp of the effects the combinations might have in the body. Some high-profile failures have ensued, most notably last year’s Phase 3 flop in melanoma, which combined pembrolizumab and a so-called IDO inhibitor, epacadostat, from Incyte (NASDAQ: [[ticker:INCY]]). The ripple effects are still being felt.
To hear what might be next for the field and for Merck, Xconomy caught up with Perlmutter at the J.P. Morgan Healthcare Conference in San Francisco last week. The following conversation has been edited and condensed.
Xconomy: Why don’t most people respond to immunotherapy, and what is Merck doing to boost those response rates?
Roger Perlmutter: There are three explanations. The first is a cancer that no immune system can see, period. In that circumstance, you’re going to have to try alkylating agents [a type of chemotherapy] or other things to change the nature of the cancer so that it becomes more recognizable to the immune system.
The second is the tumor is recognizable by an immune system, just not the patient’s immune system. In that case, immunization might be helpful. We’ve embarked upon a strategy that says, what can we immunize with, and how can we identify patients who have those characteristics?
The third is a patient’s immune system can see the tumor, but for one reason or another, just [one type of immunotherapy] isn’t enough. There’s something else you need. A lot of focus has gone into that.
Xconomy: Given all the potential options, how do you focus?
RP: Anything that is
