[Congressional Record Volume 148, Number 60 (Monday, May 13, 2002)]
[Senate]
[Pages S4273-S4274]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




                        DEVELOPING NEW MEDICINES

 Mr. DODD. Mr. President, I rise today to call the attention of 
my colleagues in the Senate to an article that appeared in the Wall 
Street Journal on May 2 which provides an important perspective on the 
challenging and vital process of developing new medicines. It is no 
coincidence that the article features Pfizer Inc., a world leader in 
pharmaceuticals and a company that made its home in my home State of 
Connecticut. Pfizer's contribution to changing the quality of health 
care by developing new therapies for conditions such as epilepsy, 
depression, arthritis, high blood pressure and more has been 
invaluable. This sort of innovation has increased the quality of care 
we deliver as well as changed the nature of it, with new medicines 
resulting in fewer trips to hospitals, doctor's offices, and better 
overall care for so many patients.
  The article details the company's efforts, ultimately unsuccessful, 
to discover, develop and test a new medicine to strengthen muscle, 
thereby helping to prevent injury and possibly osteoporosis in the 
elderly. In the process, Pfizer committed a team of scientists, $71 
million, and 10 years of effort, and this was before the development 
process even progressed to advanced clinical trials, underscoring the 
tremendous investment required in developing each new therapy. Despite 
this infusion of resources and time, the project ultimately failed to 
produce the desired therapy. But the accounting of this process in an 
excellent example of the risks, costs and efforts involved in 
innovation.
  We must continue to recognize and support these research and 
development efforts because we know the value they can provide. As we 
work in this Congress, and we must, to expand coverage and increase 
access to new medicines, we should strive to craft policy that 
continues to encourage the development of innovative products that can 
change and even save lives while helping to ensure that all our 
citizens benefit from such innovation.
  I ask that this article be printed in the Record.
  The article follows.

Drug Prices--Why They Keep Soaring--Bleeding Cash: Pfizer `Youth Pill' 
                                 . . .


                 the wall street journal via dow jones

       About a sixth of Pfizer's portfolio of drugs in development 
     were approved by Dr. Clark and his colleagues, including the 
     frailty drugs, which got the green light in December 1995. He 
     was confident the frailty compound would succeed, ranking it 
     among the top third of candidates at the time.
       But even among the fortunate drugs that pass muster 
     initially with Dr. Clark's committee, the odds remain stacked 
     against their ever making it to market. Dr. Clark's group 
     also guides the researchers, funds interim studies and 
     establishes milestones for judgment. And at any point Dr. 
     Clark's committee can kill the very projects it has approved. 
     Last year, the committee terminated research on five of seven 
     promising medicines it had previously ``canned.''
       The growth-hormone project quickly surpassed all the 
     researchers' expectations. From the time the project was 
     canned, it took only nine months to develop a drug that was 
     safe enough to test in humans--a speed record for the 
     research center in Groton, Conn., across the river from 
     administrative headquarters in New London. The drug ``had no 
     bumps or warts,'' marveled Gordon Gruetzmacher, project 
     manager for the frailty drug.
       Though increasingly optimistic, Pfizer scientists and 
     managers were sober about the challenges the potential new 
     medicine faced--especially the elusive nature of the 
     condition it was intended to treat. Frailty, which they came 
     to define as an ``age-related decline in physical 
     performance,'' wasn't a recognized disease, like osteoporosis 
     or Alzheimer's.

[[Page S4274]]

       A drug to treat the chronic condition, like many the 
     industry is now tackling, would require lengthy and 
     especially expensive clinical studies because its effects 
     might be subtle and take months or years to understand. To 
     make sure that an experimental drug deserves such a sizable 
     investment. Pfizer blends marketing with R&D early on. A 
     marketing specialist works with each drug team to ascertain 
     commercial merit. In particular, will the drug meet a 
     compelling unmet medical need and will Pfizer be able to 
     differentiate its medicines from those of its competitors?
       For the frailty drug, researchers believed they would have 
     to show that it could do more than boost hormone levels or 
     even muscle growth. Early talks with the Food and Drug 
     Administration confirmed the higher standard. Insurers, too, 
     would need evidence that the frailty drug would be worth 
     their expense.
       to persuade regulators and insurers to embrace the drug, 
     the Pfizer team aimed to prove beyond a doubt that elderly 
     people who took it could walk faster and longer and avoid the 
     kinds of falls that force many of them into nursing homes.
       Such a drug also could appeal to a younger, healthier but 
     worried market, people who might use the medicine as a 
     lifestyle enhancer, like Viagra, decades before they faced a 
     real danger of frailty. For Pfizer, a medicine to stave off 
     the ravages of old age, unlike an antibiotic taken for a 
     week, could provide a long-term revenue stream: ``People will 
     take it for 20 or 30 years--it'll be like a vitamin,'' 
     predicted John LaMattina, a senior research executive, early 
     last year.
       In late 1996, the frailty drug hit its first setback when 
     an otherwise healthy man participating in a small safety 
     study in the Netherlands developed a mysterious, mild rash. 
     The test was halted while the team investigated. The cause 
     was never found, though the leading theory remains that he 
     had a reaction to laundry detergent or hand soap. After a few 
     months, the team concluded that the drug was safe enough to 
     continue.
       Pfizer recognized the growth-hormone workers as the best 
     research team of 1996 for their trail-blazing 
     accomplishments. And they continued on the fast track, 
     initiating in late 1997 a larger clinical test of the drug, 
     involving 114 people who randomly received one of four 
     different doses or a placebo for a month. At this stage, the 
     researchers sought to substantiate the safety of the drug and 
     to pinpoint the best dose to use in subsequent tests of 
     effectiveness.
       To their happy surprise, the scientists found that even a 
     one-month regimen with the experimental drug produced 
     measurable growth of muscle. ``it was great,'' Dr. 
     Gruetzmacher recalls, ``We didn't expect an increase in less 
     than six months.''
       Though encouraging, the results didn't prove the drug was 
     working. The test could have been a fluke. Besides, increases 
     in muscle mass, even if they were real, wouldn't convince 
     regulators to approve the drug, everyone had previously 
     agreed. After lengthy discussion, the team decided to 
     propose a six-month trial of the drug to Dr. Clark and his 
     committee for approval and funding.
       But the scientists realized that showing that the drug 
     halted or reversed aging would take months or even years. Dr. 
     Clark pushed the research team to reconsider its time frame 
     and ``go for the home run'' by pursuing a longer and much 
     more expensive test that could detect subtle improvements in 
     patients' ability to function.
       The team took six months to design a trial that would 
     provide a definitive answer on whether the drug worked. They 
     eventually proposed a two-year study in elderly patients that 
     would measure muscle and some biochemical markers in the 
     bloodstream. They also would test the subjects' walking speed 
     and endurance and their ability to get in and out of a chair.
       Dr. Clark's management committee agreed to fund the study 
     in about 350 patients, much larger than usual for such an 
     early stage. To hedge the outsize bet and ensure that the 
     project was on track, the study included interim analyses at 
     six and 12 months.
       Last summer, three senior managers unconnected to the 
     project, including a statistician, were chosen to review the 
     data after six months. As outsiders, they were expected to be 
     unbiased, and they would share their findings with only a few 
     senior managers.
       In less than a week, they had reached their conclusion and 
     called Dr. Clark. He decided to break the secrecy and inform 
     the research team of the news.
       The patients taking the frailty drug had gained some muscle 
     mass--but less than 3% more than the placebo group, which had 
     also experienced muscle increases. There were no safety 
     problems with the drug. But the study was stopped within a 
     month because the drug appeared ineffective.
       Nobody is quite sure why. One theory is that the patients 
     selected for the study may have been too healthy, so there 
     was less room for improvement in the treated group. Another 
     idea is that the drug caused the pituitary gland to release 
     growth hormone in a way that was out of tune with the body's 
     system for using it.
       In the end, Dr. Clark's committee ``took pity on us,'' Dr. 
     Landshulz says, and allowed the team one last chance to 
     salvage the medicine. They were permitted to collect and 
     analyze data on the group of early patients in the study who 
     had taken the drug for a year--just in case its effectiveness 
     emerged later than six months.
       That was a long shot, everyone agreed, but worth the modest 
     incremental expense. The final analysis was completed this 
     spring, and the results were the same.
       Later this month, Dr. Clark's committee will review the 
     file one last time and officially lay to rest the frailty 
     drug, which Pfizer says cost the company $71 million to 
     research and develop.


                          The Clock Is Ticking

       Half of Pfizer's top-earning drugs face patent-expiration 
     pressure.

------------------------------------------------------------------------
                                                   Expiration     2001
                                                    of basic    revenue,
                Drug and Purpose                      U.S.         in
                                                    patents     billions
------------------------------------------------------------------------
Lipitor: Cholesterol............................         2010      $6.45
Norvasc: Blood Pressure.........................         2006       3.58
Zoloft: Depression..............................         2006       2.37
Neurontin:\1\ Epilepsy..........................   1994, 2000       1.75
Viagra: Impotence...............................         2011       1.52
Zithromax: Antibiotic...........................         2005       1.51
Celebrex:\2\ Arthritis..........................         2013   \3\ 1.16
Diflucan: Antifungal............................         2004       1.07
------------------------------------------------------------------------
\1\ Pfizer claims a separate patent concerning chemical stability of
  Neurontin protects drug until 2017
\2\ Pfizer co-promotes Celebrex for Pharmacia Corp.
\3\ Estimate.



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