Guest article provided by Dr. Karl Peace
I worked for Warner Lambert/Parke-Davis in the late 1980s and early 1990s when Tacrine, a compound that was first synthesized in the early 1940s, was selected for clinical development. The drug was discovered by Dr. Adrian Albert, an Australian, while trying to advance a new intravenous antiseptic for use by injured battlefield troops in World War II. With the successful production of penicillin by the British, Dr. Albert's efforts ended and little was heard of the drug for the next several decades.
Tacrine once again attracted acute interest when a California physician, Dr. William K. Summers, published an article in the New England Journal of Medicine (NEJM, 1986) reporting that his studies showed the compound produced marked improvements in cognitive ability and dexterity among Alzheimer's patients. A FDA report published in the same issue of the New England Journal questioned the Dr. Summers' research methods and his conclusions. However, the findings were sufficient to warrant further clinical investigation by Warner-Lambert/Parke-Davis.
Finding a treatment that improves the quality of life for sufferers of a disease that is marked by progressive mental deterioration is a challenge without equal in pharmaceutical research and development. The disease robs its many elderly victims of their final years, while their caregivers suffer tremendous emotional and financial hardships.
When I arrived at Parke-Davis, Tacrine was no longer under patent protection since it had been around for more than 25 years. However as federal law provided five years of exclusive marketing following FDA approval, it had already been elevated to clinical development status and the first clinical trial protocol had been approved. The company's hopes for producing a blockbuster drug were pinned on Cognex, the trade name for Tacrine or Tetrahydroaminoacridine. While the earliest studies did not indicate that Cognex could cure Alzheimer's or halt the relentless progression of the disease, it still held blockbuster potential if clinical studies confirmed the drug could improve the cognitive ability of patients.
The FDA CNS Advisory Committee met in July of 1991 and even though the methodology and results of our investigation were presented, the Committee again recommended that Cognex not be approved. They did however urge the company to conduct more studies using higher doses over an extended treatment time, and recommended that the drug be made available to a larger number of patients. In December 1991, FDA granted a Treatment IND (Investigational New Drug) to Warner Lambert/Parke-Davis that led to the enrollment of more than 7,000 patients.
While the expanded patient enrollment into protocols conducted under the Tacrine Treatment IND was underway in early 1992, I received a telephone call from Sally Scearce, wife of the retired, legendary, Georgia Southern basketball coach James B. Scearce.
I was saddened to learn that Coach Scearce, who had been the real estate agent in my purchase of a home for Mom in Statesboro four years earlier, had been diagnosed with Alzheimer's disease. Mrs. Scearce had apparently learned of my involvement in the Tacrine project while viewing news reports about the FDA CNS Advisory Committee deliberations on CNN and CSPAN and wanted to know if there was any possibility that her husband might receive the study medication. As the drug had not been approved at that time, Tacrine was only available by participating in clinical trials conducted under the Treatment IND. I was able to steer Mrs. Scearce to a compassionate use trial of the drug and, she later reported, it was very helpful, as Coach Scearce was able to resume many of his usual daily activities.
Parenthetically, I got to know Coach Scearce quite well when I was an undergraduate student at Georgia Southern College.
One of the 7 part-time jobs I worked to support myself, my cancer stricken mother, and my younger brother and sister, was tutor to the athletic department. I traveled with the men's basketball team in order to provide tutorial assistance to them, including Coach Scearce's son, Jimmy, when they had lengthy road trips shortly before finals. It was most comforting to me to realize that my contribution to the development of Tacrine provided a better quality of life for Coach Scearce and his family.
In March 1993, two years after the FDA Advisory committee's first rejection, the FDA recommended approval for Cognex. The agency granted marketing rights for the drug the following September. Although the additional studies were costly and mostly served to confirm the efficacy findings of the initial study, they contributed greatly to the safety information and conditions for use.
Cognex was on the market three years before the next drug for the treatment of Alzheimer's disease was approved, but it never came close to reaching blockbuster status as the company had envisioned.
--
Dr. Karl E. Peace is the Georgia Cancer Coalition Distinguished Cancer Scholar (GCCDCS), Senior Research Scientist and Professor of Biostatistics in the Jiann-Ping Hsu College of Public Health (JPHCOPH) at Georgia Southern University (GSU). He was responsible for establishing the Jiann-Ping Hsu College of Public Health – the first college of public health in the University System of GA. He is the architect of the MPH in Biostatistics and Founding Director of the Karl E. Peace Center for Biostatistics in the JPHCOPH. Dr. Peace holds the Ph.D. in Biostatistics from the Medical College of Virginia, the M.S. in Mathematics from Clemson University, the B.S. in Chemistry from Georgia Southern College, and a Health Science Certificate from Vanderbilt University.Dr. Peace’s first career was that of teaching and research at the University level. He previously taught Mathematics at Georgia Southern College, Clemson University, Virginia Commonwealth University, and Randolph-Macon College, where he was a tenured professor. He holds or has held numerous adjunct professorships: at the Medical College of Virginia, the University of Michigan, Temple University, the University of North Carolina, and Duke University.Dr. Peace’s second career was in research, technical support and management in the pharmaceutical industry. He held the positions of Senior Statistician at Burroughs-Wellcome, Manager of Clinical Statistics at A.H. Robins, Director of Research Statistics at SmithKline and French Labs, Senior Director of GI Clinical Studies, Data Management and Analysis, at G.D. Searle, and Vice President of World-Wide Technical Operations at Warner Lambert/Parke-Davis. He then founded Biopharmaceutical Research Consultants, Inc. (BRCI), where he held the positions of President, Chief Executive Officer, and Chief Scientific Officer.
