Derek B. Lowe04.05.10
I'd like to welcome everyone to the MegaPharm Target Selection and Planning meeting. We'll try to take the therapeutic areas in order, as on your agendas. Note that this year, as per the memo, we're going to actually say what's on our minds as opposed to the usual. I've been practicing in my office, and I think I'm ready to give it a try.
First, CNS. We just can't get out of this one, can we? Year after year, we keep plowing in the resources, and what comes out the other end? Press releases! Oh, and asterisks in the annual report. Look at the whole antidepressant effort and yeah, I know it's made money for us in the past, but if we run another gazillion-dollar trial that shows a 40% response in the placebo group, I'm going to need some of the NDA candidate myself. That's assuming it does anything no doubt you all caught those stories about how no antidepressants seem to actually work? That'll lower your mood right there.
Then we've got the antipsychotics. Same problem: no one knows how they work, no one's real sure which ones work and, to hear the physicians talk, every patient is practically a separate disease, anyway. Target-based drug design, oh yeah: how are you supposed to develop a drug for a condition when no one has the faintest idea what causes it? But if we're going to worry about that, then we might as well move on to Alzheimer's. What a market! What a huge unmet medical need! What a graveyard for drug candidates! Why, 25 years ago everyone was trying to get a compound that would do something about amyloid. Now it's 2010, and everyone's trying to get a compound that'll do something about amyloid. But things have still changed - now, you've got a bunch of people who aren't even sure any more if amyloid is a cause or an effect. Somebody's going to make an expensive mistake testing that suggestion out, one way or another, and who knows? It might be us.
Enough with the brain . . . you know, I like the sound of that. Maybe that should be our new motto around here. We'll take that up at the annual retreat in June. Anyway, on to Anti-Infectives. Does anyone know why we're still in this area? I mean, sure, the bugs are out there getting resistant, and they're going to come and really hand it to us at some point. But this is the only field where you can come up with the Wonder Drug of the Ages and have the FDA tell everyone not to use it. If we come up with a drug that kills off tumor cells better than anything before, it'll be king of the market. But if we make one that kills off bacteria better than anything before, it'll be locked in a vault so the bugs don't find out about it.
OK, what's next? Cardiovascular . . . ah, cardiovascular. For some reason, we still think of ourselves as a big deal in cardiovascular, but I've been racking my brains to figure out why. We're flat-out inventing ourselves out of any chance to do anything in the whole field. Blood pressure? You've got six dozen options, most of 'em generic, and good luck competing against them. And sure, I know that a renin inhibitor finally made it to market, and it only took a bunch of people all over the industry slaving away since Reagan's first term to do it. There's a cost-containment model that'll have us all living in cardboard boxes by the time we're done.
Anyway, you've got lipids, too, another area that we apparently don't know anything about. Catch that Tricor trial from Abbott? You make all the blood numbers go the way they're supposed to go, and what happens? Right, nothing at all. And you guys all remember the amount of time and money we spent on those other PPAR combinations - maybe our grandkids will figure out why they didn't work, but we're sure stuck for now. With all the statins coming off patent, you can just forget about any LDL therapy making a dime, and if you can figure out a way to raise HDL, you're smarter than I am. Even if you've got one, you're not going to be able to prove it to anyone without running a clinical trial the size of Wyoming.
You know, it's weird, but I think I'm getting the hang of this new presentation style. Up next: Allergy and Inflammation. Let's see, you've got about 10 good antihistamines out there beating each other up, so you'd better have a pretty convincing reason for being the most expensive new thing on the market. Then there are I-don't-know-how-many inhaled steroids and airway openers, some of 'em as old as dirt and with nearly as high a profit margin. So that must be why we're doing inflammation mechanisms instead. But what a tightrope! You've got the whole spectrum to deal with, from "I have a backache," to, "I just had a kidney transplant," and it's hard to tell which end your new mechanism is going to land closer to.
Now that brings us to Oncology. It was dementia that I said was like one disease per patient, wasn't it? I take it back. Cancer's the one where that really holds, and we've got plenty of proof. Five thousand orphan diseases! I don't know whether to shout "Charge!" or hide under the table when I think about it. It would help if we had some biomarkers we could trust, so we'd only give the drugs to people who had an outside chance of responding to them at all, but, well . . . does anyone have a copy of the biomarker group's presentation from back in 2005? I think someone must have sneaked into my office, deleted the files, and taken my hard copy. How many solid ones were we supposed to have a bead on by now? But hey, it's not like you can find patients for some of these things, anyway. We've got CROs knocking on doors in places I can't even pronounce trying to meet our enrollment numbers, and we're still coming up short.
There, I feel better already. Does that pretty much settle all the small-molecule programs? I don't see any hands going up. You know, what this company needs is more biologics. None of us know all that much about them, so there's not as much to be worried about, and nobody here has ever had to manufacture one, either. I have to say, that devil we don't know is looking mighty good these days, especially with the new exclusivity period. Just engineer some cells, feed 'em some ACME Cell Chow or whatever it is you put in there, wait a week and open the stopcock at the bottom of the fermentation tank . . . works for Genzyme, doesn't it? What can go wrong? Am I right, here, guys? Who's with me?
First, CNS. We just can't get out of this one, can we? Year after year, we keep plowing in the resources, and what comes out the other end? Press releases! Oh, and asterisks in the annual report. Look at the whole antidepressant effort and yeah, I know it's made money for us in the past, but if we run another gazillion-dollar trial that shows a 40% response in the placebo group, I'm going to need some of the NDA candidate myself. That's assuming it does anything no doubt you all caught those stories about how no antidepressants seem to actually work? That'll lower your mood right there.
Then we've got the antipsychotics. Same problem: no one knows how they work, no one's real sure which ones work and, to hear the physicians talk, every patient is practically a separate disease, anyway. Target-based drug design, oh yeah: how are you supposed to develop a drug for a condition when no one has the faintest idea what causes it? But if we're going to worry about that, then we might as well move on to Alzheimer's. What a market! What a huge unmet medical need! What a graveyard for drug candidates! Why, 25 years ago everyone was trying to get a compound that would do something about amyloid. Now it's 2010, and everyone's trying to get a compound that'll do something about amyloid. But things have still changed - now, you've got a bunch of people who aren't even sure any more if amyloid is a cause or an effect. Somebody's going to make an expensive mistake testing that suggestion out, one way or another, and who knows? It might be us.
Enough with the brain . . . you know, I like the sound of that. Maybe that should be our new motto around here. We'll take that up at the annual retreat in June. Anyway, on to Anti-Infectives. Does anyone know why we're still in this area? I mean, sure, the bugs are out there getting resistant, and they're going to come and really hand it to us at some point. But this is the only field where you can come up with the Wonder Drug of the Ages and have the FDA tell everyone not to use it. If we come up with a drug that kills off tumor cells better than anything before, it'll be king of the market. But if we make one that kills off bacteria better than anything before, it'll be locked in a vault so the bugs don't find out about it.
OK, what's next? Cardiovascular . . . ah, cardiovascular. For some reason, we still think of ourselves as a big deal in cardiovascular, but I've been racking my brains to figure out why. We're flat-out inventing ourselves out of any chance to do anything in the whole field. Blood pressure? You've got six dozen options, most of 'em generic, and good luck competing against them. And sure, I know that a renin inhibitor finally made it to market, and it only took a bunch of people all over the industry slaving away since Reagan's first term to do it. There's a cost-containment model that'll have us all living in cardboard boxes by the time we're done.
Anyway, you've got lipids, too, another area that we apparently don't know anything about. Catch that Tricor trial from Abbott? You make all the blood numbers go the way they're supposed to go, and what happens? Right, nothing at all. And you guys all remember the amount of time and money we spent on those other PPAR combinations - maybe our grandkids will figure out why they didn't work, but we're sure stuck for now. With all the statins coming off patent, you can just forget about any LDL therapy making a dime, and if you can figure out a way to raise HDL, you're smarter than I am. Even if you've got one, you're not going to be able to prove it to anyone without running a clinical trial the size of Wyoming.
You know, it's weird, but I think I'm getting the hang of this new presentation style. Up next: Allergy and Inflammation. Let's see, you've got about 10 good antihistamines out there beating each other up, so you'd better have a pretty convincing reason for being the most expensive new thing on the market. Then there are I-don't-know-how-many inhaled steroids and airway openers, some of 'em as old as dirt and with nearly as high a profit margin. So that must be why we're doing inflammation mechanisms instead. But what a tightrope! You've got the whole spectrum to deal with, from "I have a backache," to, "I just had a kidney transplant," and it's hard to tell which end your new mechanism is going to land closer to.
Now that brings us to Oncology. It was dementia that I said was like one disease per patient, wasn't it? I take it back. Cancer's the one where that really holds, and we've got plenty of proof. Five thousand orphan diseases! I don't know whether to shout "Charge!" or hide under the table when I think about it. It would help if we had some biomarkers we could trust, so we'd only give the drugs to people who had an outside chance of responding to them at all, but, well . . . does anyone have a copy of the biomarker group's presentation from back in 2005? I think someone must have sneaked into my office, deleted the files, and taken my hard copy. How many solid ones were we supposed to have a bead on by now? But hey, it's not like you can find patients for some of these things, anyway. We've got CROs knocking on doors in places I can't even pronounce trying to meet our enrollment numbers, and we're still coming up short.
There, I feel better already. Does that pretty much settle all the small-molecule programs? I don't see any hands going up. You know, what this company needs is more biologics. None of us know all that much about them, so there's not as much to be worried about, and nobody here has ever had to manufacture one, either. I have to say, that devil we don't know is looking mighty good these days, especially with the new exclusivity period. Just engineer some cells, feed 'em some ACME Cell Chow or whatever it is you put in there, wait a week and open the stopcock at the bottom of the fermentation tank . . . works for Genzyme, doesn't it? What can go wrong? Am I right, here, guys? Who's with me?
