immunotherapeutics, which do not fit the typical drug development paradigm, as they often involve cells rather than compounds, and show different functionalities depending on their dose and how they are combined. Many potential immune stimulants have failed standard preclinical tests run by pharmaceutical companies because singly they are not effective at the maximum tolerated dose, but there is abundant evidence that when these “failed” compounds are used with tumor vaccines at lower doses, they enhance the vaccine’s efficacy, Dr. Schlom pointed out. “But it’s alien to them—immunotherapy is still something that most pharmaceutical companies don’t want to deal with right now,” he said.

Dr. Flaherty added that “what has held back progress in this area is that individual sponsors wanted to see that they are in sight of the finish line, in terms of having an approvable drug, either as a single agent or in combination with an archival therapy—something that’s stable and static and not a moving target. But we can’t wait for each of those agents to find their home as single agents. All of these immunologics were stalled because they didn’t have single agent activity and therefore a finish line in sight.” He stressed that this thinking goes contrary to the notion of what he called “codependent targets”—targets that will only demonstrate real benefits in combination with other therapies.

Dr. Hohneker pointed out that the manufacturing and development of the biologics used in immunotherapy is not a core competency of every pharmaceutical company. Immunotherapies require a major investment of resources that some companies have not yet made, and are not willing to make until there is more proof of concept demonstrated in this area. Dr. Munos noted that the “play it safe” attitude of most pharmaceutical companies has taken industry away from making breakthroughs. “We’ve encoded so-called ‘best practices’ into standard operating procedures, hoping that this would replicate past successes, instead of finding new breakthroughs,” he said. Dr. Munos noted that the drug industry has shifted its resources away from early discovery research into late clinical trials, and suggested “bringing back the passion for R&D [research and development]. There’s hardly been a breakthrough in history that was not underpinned by a lot of passion. We need to bring that back and focus on breakthroughs, not blockbusters.” He suggested such research could be financially supported using the resources currently being spent to test compounds that are of limited clinical relevance and likely to give an incremental benefit at most.



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