February 7, 2003
The U.S. FDA has extended the labeling of Avonex® (interferon beta-1a) to include individuals who experience their first clinical episode and have MRI-detected brain lesions consistent with multiple sclerosis:
The U.S. Food and Drug Administration (FDA) has extended the labeling of Avonex (interferon beta-1a, Biogen, Inc., Cambridge, MA) to include “patients with multiple sclerosis… who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.” The FDA based its decision on the findings of the “CHAMPS” study (Jacobs, L. D., et al., N Engl J Med 2000;343:898-904).
The diagnosis of clinically definite MS requires two neurological events suggesting demyelination (loss of nerve-fiber insulation) in the brain and spinal cord separated in time and in location. Studies have shown that individuals who experience a single occurrence of a sign or symptom of demyelination and multiple clinically “silent” MRI-detected brain lesions are at high risk for developing clinically definite MS within several years. Individuals who have similar neurologic problems but no evidence of MRI-detected lesions are at relatively low risk for developing MS over the same time period.
In April 1996, Biogen initiated a multi-center, randomized, placebo-controlled clinical trial of Avonex (interferon beta-1a) for individuals who had experienced a single, isolated neurological event suggesting demyelination and who had multiple clinically “silent” MRI lesions (and thus were at high risk for developing clinically definite MS). The aim of the study was to determine if using Avonex early in demyelinating disease could delay the development of a second objective clinical sign of demyelinating disease (which would signal clinically definite MS) and to determine if treatment would have an impact on MRI-detected brain lesions. The CHAMPS (Controlled High-Risk Subjects Avonex MS Prevention Study) study was designed to take place over five years (including enrollment and three years of treatment) and included 383 individuals at 50 clinical centers in the United States and Canada.
Upon enrollment, all participants received a course of steroid treatment, which is standard therapy for treatment of isolated demyelinating clinical events and MS attacks. Then, participants began either weekly 30-microgram intramuscular injections of Avonex or an inactive placebo. Participants underwent neurologic exams at least every six months during the study; and MRI brain scans were done every six months for the first 18 months of treatment. The onset and timing of any new neurologic demyelinating events were tracked, as were adverse events and side effects.
At an interim analysis of the trial in January 2000, an independent data and safety monitoring committee determined that Avonex was safe to use in this group. (Flu-like reactions, well know with Avonex, were the most common side effects.) The committee also determined that Avonex caused a statistically significant delay of onset of clinically definite MS, determined by a delay in a second clinical attack, compared with the placebo-treated group. In addition, over the first 18 months of the study, MRI findings showed that the treatment group had a significantly lower increase in the volume of brain lesions, or damaged areas, as well as fewer new lesions. Because of its demonstrated efficacy, the committee recommended that the study be terminated prematurely. Biogen presented data from this study to the FDA in an effort to expand labeling of Avonex to include earliest demyelinating event in individuals at high risk for developing clinically definite MS.
Research suggests that damage to brain and spinal cord tissues can occur early in the disease course of multiple sclerosis. These data show that use of Avonex after a single demyelinating attack in people with multiple brain lesions can delay onset of a second attack and thus of clinically definite MS. Thus, the FDA’s approval of expanded labeling of Avonex supports earliest treatment which many believe may forestall the development of permanent clinical disabilities. This is also a signal to physicians and third-party insurers that this is an appropriate treatment for individuals with this condition.
Individuals interested in the use of Avonex for earliest demyelinating event suggestive of MS should contact their personal physicians. Additional information about Avonex can be obtained from Biogen, Inc. at: 1-800-456-2255
--Research Programs Department
© 2003 The National Multiple Sclerosis Society