Novartis must wonder what they did to deserve this one. A few years ago, it looked as if they ruled the potentially lucrative world of dipeptidylylpeptidase-IV (DPP-IV) inhibitors for diabetes. (Note - name of enzyme corrected after brain hiccup - DBL). Novartis seemed to be the first big company to come up with good chemical matter in the area, and they published a whole string of papers while their lead compound went through the clinic.
Then came trouble. Merck turned out to have a big program of their own in the area, which in Merckian fashion they’d kept very quiet about, and they actually beat Novartis to the FDA. And then they beat them to market, because the agency had some questions about the Novartis compound. Those questions have done nothing but multiply. Now the problem appears to be liver tox, one of the last things the diabetic population needs. It’s looking very likely that Novartis’s compound may never get to the market in the US at all.
So here’s a question: if both compounds had made it to market, wouldn’t the people who tally up lists of “me-too” drugs have considered the first compound (from Merck) to be the original, and the Novartis one to be the copycat? After all, they target the same enzyme for the same disease in the same way. (I should mention that a DPP-IV inhibitor itself is just the sort of thing the industry is supposed to be turning out, a completely new way to treat a major and growing public health problem, but we'll pass over that for now).
But these compounds were developed more or less simultaneously, with the two companies racing each other to the market. It’s not like either company sat back and watched the big profits roll in, and said “I need to latch on to some of that – let’s make one of those, too.” The whole thing was done on a risk basis, because while the biochemical rationale behind DPP-IV inhibition makes sense, a lot of things make sense and still go nowhere. No one really knew how the drugs would perform, either in the clinic or in the marketplace.
And take a look at the problems that the Novartis compound has. Like so many other toxicology hits, these came out of the cloudless sky. Well, actually, it’s more accurate to say that the sky over the toxicologists is never cloudless, because you never know what’s going to happen. In this case, Novartis has taken an especially painful and expensive beating, since the drug had advanced so far before the problems began to make themselves clear.
I’d like to ask some of the critics of the industry what they think about this situation. Me-too drugs are a particular arguing point with many of these people, so here we go: does that term apply in this case? If not, then why not? Should companies go after the same target in the same way at the same time? If not, then why not? How do we deal with the fact that any compound can fail at any time, other than turning companies loose to compete with each other and take as many shots at a target as possible? Do you have a better solution – and if not, well, then, why not?