No Alastair, none of those points are arguments for incentives for investment in drug development and testing under the European model.
They are reasons people might want to have new drugs, even specifically reasons why new drugs might save some people money, but they are not incentives for the drug companies to develop and test drugs. Doubling or tripling survival time is great, but unless the drug companies can charge for that benefit, it doesn't do a lot to motivate investment by them.
Phase II trials pretty much tell if the drug will work as planned and if it is an improvement on current drugs.
A lot of the cost is to develop the drug, and do phase I and phase II trials. Also you don't always find out that the drug will work better at the conclusion of phase II. In fact sometimes you can't be really certain it worked better until after its been on the market for years, or we might not even know for sure ever.
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...Steve Paul lamented at our recent PSA meeting that Phase III is "still pretty lousy," in terms of attrition rates -- around 50%. And not always for the reasons you'd expect. "You shouldn't be losing Phase III molecules for lack of efficacy," he said, but it's happening throughout the industry. (If you missed it, a recap of the PSA goings-on will be in the next IN VIVO.)
But we would expect these failures to come mostly from pharma's home-grown crop of drug candidates, not so much from the drugs accessed via high-priced biotech collaborations...
invivoblog.blogspot.com
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Maribavir, Ouch
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Posted by Derek
Viropharma has announced that their Phase III trial of maribavir, a compound targeting cytomegalovirus, failed big-time. Well, they didn't used the term "big-time", but they might as well have. The treatment group (patients with recent bone marrow transplants) showed no difference in CMV infection rates compared to placebo. This is especially disappointing, considering that the compound looked pretty good in Phase II. That's a useful lesson in the difference between Phase II and the real world...
pipeline.corante.com
Rolofylline Hits the Skids
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Posted by Derek
There is no good way to spin a Phase III failure. By then you've made it past the main reasons for a drug to wipe out (PK and total mechanistic failure). A breakdown at this stage is a more subtle affair (well, except for the money involved, which is not subtle at all). For example, a drug might show efficacy in a carefully constructed Phase II trial, but can't perform under the wider (and more realistic) conditions of Phase III.
That's what appears to have happened to Merck's MK-7418 (rolofylline, formerly KW-3902). This adenosine A1 antagonist, which Merck picked up by buying NovaCardia a couple of years ago, was being developed for acute heart failure. That's a tough indication, and this isn't going to improve that reputation. (This Forbes piece has a tour of the pile of discards that this area has become over the years. Rolofylline looked as if it might work in Phase II, but (from what I can tell from the press releases) missed every endpoint in Phase III...
pipeline.corante.com
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Arzoxifene: Not the Road to Big Profits?
Posted by Derek
Eli Lilly announced some bad news last week when they dropped arzoxifene, a once-promising osteoporosis treatment (and successor to Evista (raloxifene), which has been one of the company's big successes).
If this drug had been found ten or fifteen years ago, it might have made it though. But the trial data showed that while it made its primary endpoints (reducing vertebral fractures, for example), it missed several secondary ones (such as, well, non-vertebral fractures). And the side effect profile wasn't good, either. That combination meant that the drug was going to face at hard time at the FDA for starters, and even if it somehow got through, it would face a hard time competing with generic Fosamax (and Lilly's own Evista).
So down it went, and it sound like the right decision to make. Unfortunately, given the complexities of estrogen receptor signaling, the clinic is the only place that you can find out about such things. And there are no short, inexpensive clinical trials in osteoporosis, so the company had to run one of the big, expensive ones only to find out that arzoxifene didn't quite measure up. That's why this is a territory for the deep-pocketed, or (at the very least) for those who hope to do a deal with them at the first opportunity.
One more point is worth emphasizing. Take a look at the structures of the two compounds (from those Wikipedia links in the first paragraph). Pretty darn similar, aren't they? Arzoxifene is clearly a follow-up drug in every way - modified a bit here and there, but absolutely in the same family. A "me-too" drug, in other words, an attempt to come up with something that works similarly but sands off some of the rough edges of the previous compound. But anyone who thinks that development of a follow-up compound is easy - and a lot of people outside the industry do - should consider what happened to this one.
pipeline.corante.com |
