Pfizer experimental compounds being investigated for utility in malaria, SARS, smallpox
NEW YORK, N.Y., June 26, 2003 -- Pfizer Inc reported that a number of the company's compounds have shown activity against some of the world's leading infectious diseases -- malaria, severe acute respiratory syndrome (SARS), and pox viruses.
The research programs involve compounds discovered by Pfizer scientists that range from a marketed medicine -- the leading antibiotic Zithromax -- to untested molecules selected from the company's vast chemical library.
- Phase II clinical trials against drug-resistant malaria using a combination of Zithromax and chloroquine, an older, commonly used malaria treatment, have shown very promising results. The combination has been shown to be three times more effective than chloroquine alone. Based on these encouraging data, Pfizer plans to conduct much larger, Phase III clinical trials worldwide.
- At least 10 Pfizer compounds have shown significant activity against the SARS virus in laboratory tests. The company will now selected the best candidates for continuing development and potential studies in humans.
- Pfizer said it has shared an experimental medicine with Harvard Medical School because of potential utility in treating smallpox.
"Taken together, we are making inroads against three of the world's most-feared diseases," said Pfizer Chairman and Chief Executive Hank McKinnell. "We are able to do because our scientific operations are unmatched in their global scale. With more than two million compounds in our research library and the ultra-high throughput systems to rapidly screen them against diseases, we have a very good chance of emerging with at least some credible candidates against these and other unexpected threats."
For malaria, Pfizer will begin Phase III clinical trials, the final stage of human testing, on three continents to definitively demonstrate the efficacy of Zithromax combined with chloroquine. Pfizer cautioned that there are no guarantees that any of these compounds will result in a viable medicine for patients.
"There are tremendous risks and high costs involved in any pharmaceutical research and development project," McKinnell said. "The complexity of this research is enormous, and my best guess is that none of these candidates has a significant commercial market. But the human stakes are so high that we must continue our investment and seek partnerships through all phases of development and distribution if we are to save lives."
Zithromax/Chloroquine combination against malaria
Plasmodium falciparum is the most common form of malaria -- a mosquito-borne disease that affects 300 million people worldwide and results in approximately 1.5 million deaths each year. "If untreated, it can cause cerebral malaria and death," said Dr Solomon Nwaka Scientific Officer and Project Manager at the Medicines for Malaria Venture, a not-for-profit organization founded by the World Health Organization and other agencies.
"This is a global crisis that is becoming more alarming with increased resistance to older drugs," he said. "We desperately need new scientific approaches, increased investment and collaboration between industry, governments and academic medicine. In this regard, the chloroquine/Zithromax combination Phase III clinical trials represent an important scientific undertaking."
Chloroquine, introduced more than 30 years ago, remains a standard treatment. But because the malaria parasite has developed resistance against chloroquine, the medicine now is often ineffective.
Pfizer scientists set out to find a more potent therapy. They found that 28 days after taking chloroquine, only 31 percent of patients were free of symptoms. That number was slightly higher -- 38 percent -- when patients were given Zithromax. But when the two medicines were combined, the success rose to 96 percent.
Dr. Mike Dunne, who is leading Pfizer's development efforts, said larger-scale clinical trials are planned and will involve over 1200 patients in India, Indonesia, Kenya, Peru and South Africa, all countries where the prevalence of malaria is high. Pfizer has begun discussions about the program with officials in these countries and with the U.S. Food and Drug Administration.
[Pfizer recognizes the commercial prospects for this medicine are limited. The company said it intends to make the medicines available to those in need in the developing world using models developed for other Pfizer access programs.]
Pfizer compounds act against SARS virus
Pfizer's laboratories at La Jolla, Calif., have provided 350 anti-viral compounds for testing against SARS to the National Institute of Allergy and Infectious Diseases and the U.S. Army Medical Research Institute of Infectious Diseases.
"Last month, we reported that some of our compounds showed activity against the SARS virus," said Dr. Dave Matthews distinguished research fellow at Pfizer's R&D site in La Jolla, California. "Since then, we have sent many more for laboratory testing and found some that are five times more effective."
The SARS virus has a key protein required for replication that is related to a protein in rhinovirus, primary cause of the common cold. In an earlier search for a cold treatment, Pfizer scientists looked at the molecular structure of this key rhinovirus protease and found compounds that stop reproduction. X-ray crystallography, which visualizes individual atoms, shows how these compounds bind to enzymes that control replication and make them inactive. It was the realization that the rhinovirus and SARS virus proteases have similar structure and function that originally led Pfizer scientists to test selected rhinovirus inhibitors against SARS.
"We are very encouraged," Dr. Matthews said. "We believe we can now go forward with one or two of the most promising candidates. We know a lot about these compounds. But first, we will conduct animal studies to ensure that there are no unforeseen risks. If these studies are successful, we will design further studies in humans."
Dr. Peter Corr, senior vice president, Science and Technology, Pfizer, said the projects involving SARS and malaria include strong partnerships with governments, leading academic institutions and public health organizations. Pfizer's global capabilities allow the company to share its findings with other organizations to rapidly advance development.
As one example, Dr. Corr said Harvard Medical School approached Pfizer to request one of the company's experimental medicines for research in smallpox. "We sent the first sample on the day the request came in," Dr. Corr said. "This can be a deadly disease, and immunity through vaccination is waning throughout the world and we're all concerned about the threat of bioterrorism."
Dr. Corr stressed that the smallpox research is at a very early stage. "We could move forward with human testing of a compound in the near future. Our ability to quickly respond to these diseases and threats is based on the vast R&D infrastructure supported by a vibrant pharmaceutical market that encourages innovation."
Pfizer has approximately 14,000 researchers worldwide at major research facilities in the United States, Europe and Japan. Pfizer and partner organizations currently fund and operate innovative health care programs in the developing world. Among them is the International Trachoma Initiative, which has reduced the incidence of active infection by over 90 percent in Morocco, 50 percent in Tanzania, 75 percent in Vietnam and 45 percent in Ghana. To date, Pfizer has donated over $250 million worth of Zithromax to the ITI.
Through the Diflucan Partnership Program, Pfizer provides its antifungal medicine, Diflucan, free of charge to governments and non-governmental organizations to treat opportunistic infections in HIV/AIDS patients. The program, which currently operates in 17 countries, also provides for secure distribution and training for healthcare professionals.
Posted: June 2003
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