Why so many Surprising Disappointments from Pharmaceutical R & D?

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

Five Predictions for the Pharmaceutical Industry

I don’t pretend to have a crystal ball but trends and evolving patterns can lead one to predict pretty accurately what is going to happen in the future.  As the predictions in Pharmaplasia have pretty much come to pass and continue to play out,  I decided to take another shot at formulating what appears to be in store for the pharmaceutical industry over the next five to ten years.  So here goes…

  • Big Pharma investors will become less tolerant of multi-billion dollar mega-acquisitions of companies and technologies that benefit executives, bankers, and lawyers but do little to improve the acquiring company.  Investors will no longer accept excuses when these overpriced deals don’t deliver on the expectations and promised returns.
  • Biotech investment will continue to decline as investors become increasingly rigorous in their due diligence, identifying true innovation with meaningful clinical potential rather than investing hopefully in purported innovation hyped by articulate CEOs looking to win the “buy-out lottery.”  With the first prediction in play, there will be fewer “buy-out lotteries” to be won.
  • The continued product focus of pharmaceutical R& D is leading to a prolonged period of fewer truly innovative clinically important new treatments.  The acquisition opportunities for development-ready, truly innovative technologies in small biotech companies will slow dramatically.   And,  merely shooting at “disease targets” with chemistry, without a comprehensive understanding of the pathophysiology of disease, leads to a “hit and miss” mentality, lacking in appreciation for the complexities of human biology.
  • The market will continue to experience significant drug shortages until the healthcare market is willing to pay prices that support high quality cGMP-compliant manufacturing and the pharmaceutical industry (including generic drug companies) realizes that high quality cGMP-compliant manufacturing is a critical success factor, important enough to make the necessary investments to consistently sustain it.  This is difficult for Pharma executives because manufacturing has always been the place to look for operational cost cutting and investment in manufacturing expertise and systems is not as “sexy” or newsworthy as placing a big bet on a “hyped up” new drug technology to excite Wall Street analysts.
  • Unfortunately, the pharmaceutical industry will not have the necessary experience base or leadership to navigate this perilous journey.  Downsizings, retirements, and industry changing career choices have diminished the necessary operational (think research and manufacturing) experience and expertise from the industry.   And, those who have survived and aspire to take on leadership roles have mentored during a period characterized by “me too” drug and acquisition driven R & D, questionable (if not illegal) marketing and sales tactics, and a corporate priority for investor interests over patient well-being.   Not exactly the development track you’d prescribe given the organizational challenges  and the complexities of the evolving healthcare market these new leaders will face.

Realistically facing the prospects for the future can help identify opportunities for changing what isn’t working and developing plans to take corrective action, if necessary.  If you don’t believe my predictions are valid, or you believe I have been to negative, then there is nothing to change.  Big Pharma can continue doing what it is doing.   Seems to me  that’s been the consensus position for some time now.

mike@pharmareform.com