Archive for May 2011
Pfizer’s new CEO, Ian Read, recently discussed his plans for reinvigorating the company’s R&D performance. He spoke of getting “an entrepreneurial sense into the organization with empowered, committed scientists that are focused on what I would call making unstoppable products, shots IN goal not shots ON goal…”
“Unstoppable products,” “shots in goal,” “shots on goal” – what does this all mean and how will it impact R&D productivity?
“Shots on goal” is a term obviously derived from sports. In theory, you have a better chance to score goals in hockey by taking 20 shots as opposed to taking only 10. Of course, they need to be GOOD shots and not just wild attempts taken blindly. Each shot is taken not just to get it on goal, but rather to get it in goal. Thus, it would be a bit strange to hear a hockey coach differentiate between “shots in goal” and “shots on goal.” Every hockey player takes each shot fully intending to score.
The “shots on goal” philosophy in drug discovery emerged from the realization that, no matter how good your research tools are, animal models such as genetically modified mice are very limited and are not necessarily good predictors of beneficial activity in humans. It is virtually impossible to predict whether a new discovery drug candidate will be a success or failure. There are a number of reasons for this. Does the new compound have an inherent unforeseen toxicological effect? Is the new mechanism being studied having fewer beneficial effects in patients than expected? Oftentimes, the true effects of drugs are only learned when they are tested in people. The unraveling of the human genome was a great boon to discovery scientists; it yielded a wealth of hypotheses as to how to go about treating, or even curing, a variety of diseases. The problem, however, was that while many of these new targets looked very promising in the lab, it was unclear as to which would translate into effective therapeutic treatments for patients. In vitro tests and animal testing often provided tantalizing results, but no guarantees.
The “shots on goal” philosophy was applied in the Pfizer oncology labs in the late ‘90s and early ‘00s as a result of the explosion of new targets that were emerging. At that time, there was a plethora of new ideas to explore in pursuit of discovering new treatments for cancer – some ideas were based on how to prevent tumor cells from metastasizing, others were focused on preventing tumors from growing blood vessels so they would starve themselves and die, some were specific to blocking the processes that caused tumors to grow wildly and still other approaches were even designed to help one’s own immune system fight off this awful disease. All of these were exciting, viable ideas. However, it was impossible to believe that any one of these would be a “magic bullet” to cure cancer. Furthermore, it was impossible to determine which approaches would be superior to others. The decision was made to find good compounds based on each idea and then take these compounds into clinical trials to see which, if any, successfully treated cancer. To be successful in the fight against cancer, a number of strategies—or “shots on goal”—were needed.
The ones taking these shots were in the Pfizer cancer discovery group, which grew to over 200 people making it one of the largest divisions in the company. Over a ten-year period, it produced a number of clinical candidates that explored over 20 of these novel ideas to treat cancer. While many of these compounds failed to improve the survival of cancer patients, a number of them proved to be very effective. Two of these compounds have already reached the market, Sutent and Tarceva. Others, including axitinib and crizotinib, are in the final stages of testing and are generating a lot of excitement in the clinical community. In fact, it can be argued that Pfizer has the best oncology pipeline in the industry. Yet, at the start of every one of these programs, one could have rationalized why they might not be successful—or why that “shot” shouldn’t have been taken.
One might think that the “shots on goal” method is a scattershot approach, which, at best, yields a lucky result and at worse, bloats the industry and inflates drug prices. Actually, it is a valuable R&D philosophy that has its foundation in the belief that you can’t pick winners without clinical data and a product doesn’t become “unstoppable” until its full efficacy and safety profile are understood. However, for this philosophy to be successful, you must be certain that the “shots” are compounds that have cleared stringent hurdles designed to maximize their potential for success in the key clinical trials in patients. Just as a hockey coach puts his team in a position to win by encouraging his players to bombard the goal with good shots, a research manager increases his team’s chances for success by exploring multiple promising drug candidates in the clinic.
The “shots on goal” philosophy is one designed for success, meant to maximize the overall productivity of an R&D organization. Every “shot ON goal” is made with the full intent of it being a “shot IN goal.” Former Pfizer CEO Hank McKinnell used to say that he didn’t need to go to Las Vegas to gamble – he was already gambling enough on R&D. The business of successfully discovering and developing new medicines is an incredibly risky endeavor, one that requires a lot of attempts before a winner is found. Limiting your shots by assuming that you can predict winners may ultimately prove to be a flawed strategy.
On his May 12th show, Dr. Oz recommended to his viewers that they always use a generic drug because, in general, such a drug has been given to a great many patients and more is known about its safety than a newer prescription medication. Ironically, Dr. Oz opened this same show talking about recent safety concerns that have arisen over the use of Alli. The active ingredient in Alli is orlistat, a drug discovered by Roche and sold under the trade name Xenical. The patent on orlistat has expired, so technically it is a generic drug. Clearly, Dr. Oz’s suggestion that generic drugs are safer is an oversimplification. His contradiction highlights the fact that the public needs to be better informed about what a generic drug is.
When a drug company invents a new medicine and has it approved by the FDA, it has a patent on the new medicine that allows this company an exclusive period of time (generally 10 – 12 years) during which it is the only company that can sell the drug. Once the patent for this medicine expires, it “goes generic” – that is, anyone can get approval from the FDA to make and sell this drug. In fact, the vast majority of prescriptions written every year are for generic drugs.
But just because a drug reaches generic status doesn’t automatically make it universally safe. It just means that its patent has expired and it can be made by a lot of other companies. Because it has been on the market for a number of years, more is understood about the risk-benefit profile of the medication at this point than when it was first marketed. However, the safety profile of the compound doesn’t change. As a generic, it still has the same side-effects it had when it was a branded drug. A great example of this is acetaminophen, the active ingredient in Tylenol. There is no difference between Tylenol, the branded drug, and acetaminophen sold under the name of the pharmacy you might use such as CVS. Acetaminophen has been taken by hundreds of millions of people around the world over the last 50 years. You can buy it in any drug store and most supermarkets. More is known about it than most prescription medications. And yet acetaminophen is the leading cause of calls to Poison Control Centers every year (>100,000). Acetaminophen accounts for more than 56,000 emergency room visits, 2,600 hospitalizations and an estimated 458 deaths annually as a result of acute liver failure. These incidents are largely due to overdoses of this drug, both intentional and unintentional.
So, the bottom line is that every medicine can cause a safety problem in people. It is impossible for a drug to be universally safe in males and females, old and young, people of different ethnic backgrounds, etc. People should only turn to medicines as a last resort. Lifestyle changes, diet and exercise are the sorts of things people should do before turning to pills. And when people do need to turn to medicines to alleviate their illness, they should discuss with their doctor the potential side-effects that the prescribed medication has. Yet, despite all of these caveats, medicines save lives, prevent serious debilitating diseases and improve the lives of millions of people each year.
Why do people who attack the drug industry make doctors out to be stupid?
My experience with the Dr. Oz Show is now done. I watched the show that contained my appearance today and I came away with a variety of feelings. First, while I appreciate the need to edit a show like this, I was disappointed that a few important points which I made were taken out. To be fair, the final cut did include a number of issues that I wanted to address. Yet, what was again hammered home to me in watching the segment titled “The 4 Secrets That Drug Companies Don’t Want You To Know About” is the little respect that doctors are given in the healthcare process.
I have a tremendous respect for doctors. It is incredibly difficult to get into medical school and so the academic credentials of med students are stellar. Then, they go through four years of medical school and another 3+ years of residency and then another year or more of study on a fellowship in their specialty. Only very talented and dedicated people get to be a part of this profession. And yet, to hear drug critics talk, you’d think that a doctor has little knowledge of diseases and that they are at the mercy of a drug rep to teach them the latest medicine. The critics make it seem that a doctor is only too eager to prescribe a new medicine especially when a drug rep offers them a free pen and pizza for lunch. Finally, a doctor apparently turns weak-kneed when a patient comes in and asks for a new drug as they are unable to say no to such requests.
Well, my experience is a lot different. Doctors are very skeptical of new medicines. And why shouldn’t they be? They are smart individuals who have a great deal of experience in treating their patients. They attend scientific meetings in their specialty and read the latest medical journals. They know the strengths and weaknesses of the medicines they prescribe and they know their patients’ conditions and needs. They also know that a major priority is “to do no harm.” Why would they switch to something new when they are already successfully treating their patients with effective medicines?
Doctors seek new medicines for conditions where no treatment exists. They will be interested in a new medicine when current treatments do not work for some of their patients. They will also be interested in a new drug if it has advantages over older ones. BUT THEY ARE THE GATEKEEPER FOR THE MEDICINES THAT THEIR PATIENTS GET. It is not the drug company, it is not the drug rep, it is not really the FDA. Ultimately, doctors decide in consultation with their patients. It is this relationship that determines if new medicines have value. No amount of advertising or free drug samples should change this. To imply otherwise is to insult the entire medical profession.
John L. LaMattina, PhD, retired as president of Pfizer Global Research and Development in 2007 where he managed more than 13,000 scientists and support professionals in the United States, Europe, and Asia. Dr. LaMattina has received numerous awards including an Honorary Doctor of Science degree from the University of New Hampshire. He is also the author of DRUG TRUTHS: DISPELLING THE MYTHS ABOUT PHARMA R&D and a senior partner at PureTech Ventures.