Friday, Dec 21, 1990

HHS News U.S. Department of Health and Human Services

Washington D.C. -- December 21, 1990 --

The Food and Drug Administration today announced approval of a treatment for a chronic hereditary immune disorder that strikes young people, mostly men and boys, and leaves them susceptible to infections.

In the disorder, called chronic granulomatous disease or CGD, the white blood cells are unable to fight infections. The new therapy -- the first approved genetically engineered form of the naturally occurring protein called gamma interferon -- appears to boost the white cells' effectiveness.

The therapy will be injected three times a week in most cases.

HHS Secretary Louis W. Sullivan, M.D., said, "Most CGD patients are male children or adolescents who have inherited this disorder as an X-linked recessive gene. They suffer frequent life-threatening bouts of bacterial and fungal infections, often requiring hospitalization, that traditionally could be treated only with high-dose antibiotic therapy. With the use of gamma interferon, we can now expect patients to have a more normal day-to-day life."

HHS Assistant Secretary for Health James O. Mason, M.D., who heads the Public Health Service, said, "CGD affects fewer than 400 Americans. An impressive cooperative effort between federal health agencies and industry have made this revolutionary new biological drug available to them. Major components of the clinical trials were carried out by John I. Gallin, M.D., director of the division of intramural research and his colleagues at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, where the disease has been under study for almost 20 years. Further developmental efforts toward testing and commercial production were conducted under "orphan drug" status granted by FDA to Genentech, Inc. of Sou; San Francisco, Calif. In addition, the product was evaluated and approved by FDA in less than a year."

Dr. Mason added, "The actual CGD disease process, like many inherited immune disorders, remains a mystery. In these patients, their phagocyte cells can ingest bacteria but can't kill them. Thus the patients are highly susceptible to infection with common pathogens such as staphylococcus, pseudomonas and other organisms that rarely cause clinical complications in people with normal immune systems. Scientists think that gamma interferon enables the phagocyte cells, though defective, to kill invading infectious organisms."

Modern supportive therapy has increased the life expectancy of people with CGD, but about 80 percent of children diagnosed with the defect suffer unusually frequent or severe infections before the second year of life. These infections in some cases may retard normal development or lead to death.

Gamma interferon is naturally produced in minute quantities by the body in certain types of white blood cells to help fight off infection. This protein has now been copied and produced commercially using Escherichia coli -- a harmless bacteria -- using recombinant technology methods. Recombinant alfa interferon was first marketed for a rare form of leukemia in 1986, but alfa interferon is virtually unrelated to gamma interferon expect for its antiviral activity.

In randomized, placebo-controlled clinical trials conducted to determine the effectiveness of gamma interferon in the prevention of serious infections in CGD patients, a 67 percent reduction in serious infections in patients receiving the drug -- compared to those receiving placebo (an inert substance) -- was reported. Most of the patients in the trial also received prophylactic antibiotics. These trials, involving 128 subjects, were carried out at 10 centers in the United States and three in Europe. The largest share of patients (28) were treated at NIAID.*

Side effects observed in these trials, including headache, fever, rashes and chills, were common but transient. The long-term effects of the drug on normal growth and development are unknown, and gamma interferon has been shown to induce miscarriages in animals. Postmarketing studies will be conducted by the manufacturer to determine long-term effects. The drug's labeling will advise physicians that the drug should not be used during pregnancy unless the benefits clearly outweigh potential risks.

Gamma interferon is injected under the skin three times a week. It will be supplied by the manufacturer as a single dose vial that can be used for home administration. It will be marketed by Genentech, Inc., under the brand name Actimmune.

*Among the study's other collaborating investigators are Drs. R.S. Weening, Emma Children's Hospital and Academic Medical Center, Amsterdam, The Netherlands; J.T. Curnutte, Scripps Clinic and Research Foundation, La Jolla, Calif.; P.G. Quie, University of Minnesota Medical School, Minneapolis; and R.A.B. Ezekowitz, Harvard Medical School, Children's Hospital, Boston, Mass.

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