FDA rejections of new drug applications (insufficient efficacy or safety data), totally unexpected drug failures in Phase III trials, bewildering “no significant differences” demonstrated in comparative trials, eye opening safety issues in late stage trials or raised by FDA Advisory Boards. In many cases, negative results sufficient to delay approval if not “kill the drug.”
Along with these stories come the unscientific rationalizations of failures. “That’s drug development.” “High risk, high reward.” “Biology is complicated.” “Diseases we are trying to treat today are far more complex.”
These are not new headlines for the pharmaceutical industry. In fact, and unfortunately, they have almost become a cultural industry expectation. Patients ride the roller-coaster of hope and disappointment while investors, also frustrated, keep hoping for that occasional “big win” that makes it all worthwhile.
The pharmaceutical and biotech industries have to find a better R & D model before patients lose faith and investors no longer feel that the “drug discovery and development lottery” is worth playing.
How many more times can Big Pharma place big bets on “promising“ compounds with limited “proof of concept” only to find out they have been sold worthless technology that can’t even make it through a traditional development program to gain market approval?
How many Pharma pipelines boast the number of compounds in development merely to demonstrate that they have something worth investing in, while knowing full well most of the compounds have little or no chance of really making it to market or producing a profit?
How many compounds in these Pharma pipelines (or biotech compounds for that matter) have been strategically developed so as to embellish the efficacy “potential” without exposing or exploring the design flaws that might compromise this “potential?” How many of these compounds have been carefully tested so as to avoid any suggestions of toxicity that might be difficult to explain or might raise concerns during a “Big Pharma due diligence” (for biotech) or worse, during a regulatory review?
But many of you might be thinking…well that’s just the way pharmaceutical and biotech R & D is. Well, you’re right… it is and it has worked for decades when the benefits of drug treatment (versus no treatment) outweighed the risks and the market was far more receptive to paying for mediocre “follow-on” products?
Find a compound with biologic activity (remember “get a hit in high throughput screening?”), see if it causes any “apparent toxicity” (do the regulatory required testing but don’t look too hard beyond that) in a few animal models. Do a quick Phase I trial to see if it causes any “apparent toxicity” in a few volunteers. Your objective is to get into and out of Phase II (not to really understand what happens in Phase I or II). Now, pick a dosage schedule and the easiest, fastest indication to establish a quick proof of concept. Then, if you’re a biotech company, find a Big Pharma to buy your compound and/or your company. If no buyer, get more investment to start a Phase III trial. If you’re a Big Pharma, push it into full-blown Phase III clinical trials as fast as possible on a timeline that shows investors your “quick to market” development strategy and then “hope for the best.”
The problem is that this historical Pharmaceutical/Biotech R & D model is no longer viable. So what has to change? mike@pharmareform.com
