AN-P-chn2

Andreas Persidis, CEO

Drug combinations: sometimes they work well (see for example BMS’s recently reported results on the Yervoy and Opdivo combination for melanoma), sometimes they fail. Yet, whatever the early evidence, drug combinations deserve a very close look for two reasons:

First, developing a regimen based on a “multi-dimensional strategy” that hits more than one targets, reflects better the biological reality of how complex diseases work (multiple pathways, feedback loops etc.). The small-molecule single-target approach has yielded some impressive results but relies on some strong assumptions about the complete role of that target which we ignore “at our own peril”. The peril is of course the possibility of drug side effects or reduced efficacy.

On the other hand, fighting a disease through multiple carefully selected pathways could be more effective and allow lower doses of each combination constituent, hence possibly leading to fewer side effects. It’s like being attacked by an entire beehive: any single sting does not kill you but when you get hit by thousands of bees you can get seriously injured. Let’s call this the “attacking beehive” therapeutic strategy.

Second, a combination therapy seems more compatible with the current state of our knowledge of diseases, knowledge that is often incomplete and contradictory. If you are not 100% knowledgeable of how exactly a disease works, isn’t it a safer bet to attempt to modulate to a lesser degree a selected set of relevant pathways, than to go after a single target in a big way?

But it’s not just about the science. There are at least two business reasons why combination therapies sound like a good idea:

  • First, successful combinations could be the basis for targeted therapies, product differentiation and hence financial viability.
  • Second, combinations need not consist exclusively of new and/or expensive drugs and so this could help contain the cost. A drug repositioning mindset could therefore have an important role here.

Developing combination therapies is not without it’s challenges though:

For it to succeed, we would need to re-engineer the medicines development process making it more adaptive and more combination-therapy friendly. We would also need to figure out workable models for two or more pharma to divide the proceeds of a combination therapy. Yet this might be a better investment that M&As, pipeline swaps etc., activities that do not increase the overall pie but merely redistribute the existing one.

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