Should companies focus on big markets and the blockbuster dream? The more modern approaches are not without risks, says Derek Lowe

There is no shortage of strategies for drug companies to follow as they try to bring compounds to market. It’s been fashionable for several years now to look down on the ’blockbuster mentality’ of always trying to go for the biggest drugs in the biggest markets. And there’s a lot to look down on, although I can’t help but think that some of the people who talk this way would also not turn down such a drug should it appear!


Blockbusters to speciality markets to personalised medicine - a trend?

The blockbuster drugs gave us the industry we have today, and whether that’s a good thing is the first place that the arguing starts. Since all our compounds are wasting assets, with ever-ticking patent clocks, a huge successful drug can, as with an over-fertilised lawn, produce unsustainable growth and terrible re-adjustments when its source is taken away. The usual response has been ’well, go find yourself another blockbuster’, and there you have the problem.

Part of that problem is the need for blockbuster indications. That was fine in the earlier days of, say, the cardiovascular field, with millions upon millions of people needing their blood pressure reduced and their cholesterol lowered. But to find an unmet need of this size now you have to look to things like Alzheimer’s disease, the biology of which is rather less well worked out. The people over at Eli Lilly could tell you more about that, although they probably aren’t in the mood to, having just had a viciously expensive Phase III failure in this area.

This latest disaster is one reason why Bernard Munos, recently retired from Lilly and author of several widely cited papers on drug development strategy, is now telling people to stay away from such fields altogether. His advice is: if your drug is going to need a big Phase III trial just to prove that it works at all, you’re probably better off not taking the risk (especially in an area like Alzheimer’s, where the biologists are all still yelling at each other). Look instead for smaller indications that can be pinned down more firmly in Phase II.

So in recent years there’s been more of a focus on smaller, but still very lucrative, speciality markets. Oncology drugs are a perfect example. The problem of course is that there are fewer patients so the price of the drug has to go up to get the same returns. But when you charge more, people expect better results, and developing really good drugs is difficult, no matter what their market size. 

If you take this process further, you get to Genzyme’s market niche, with treatments for syndromes like Fabry disease and Gaucher. These are really quite obscure - it’s safe to say that the only thing most people in the drug industry know about either of these diseases is that Genzyme makes drugs for them. For the patient, the cost is high (there are few higher), but the benefit is huge. The only problem with this business model is if someone else moves into the same space. That’s recently happened with Gaucher disease, with the entry of a competing enzyme from Shire and a Pfizer-Protalix collaboration set to join them soon. Genzyme has such a hold on this patient population that at least one of these drugs may well have to compete on price.

The reductio ad absurdum  to this line of thinking – well, nearly absurdum  but not quite – is a completely personalised therapy, such as a cancer vaccine. The science isn’t there yet, but it could yet fall into place, and then what? We’d have a different drug for every single patient. An amazingly expensive one, it’s safe to assume - but one that might hold a good chance for a complete cure. The world’s regulatory agencies are not equipped to deal with that situation, at least not yet, and you have to wonder if the world’s health insurance companies are ready, either. They’re having enough of a time as things stand, and so are we, just trying to find things that they’ll pay for.  

Derek Lowe is a medicinal chemist working on preclinical drug discovery in the US