Baxter International Inc today reported topline results of a phase 3 trial of intravenous immunoglobulin (IVIG, Gammagard) showing the treatment failed to meet co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer's disease.
The results are from the Gammaglobulin Alzheimer's Partnership (GAP) study, conducted by Baxter in collaboration with the Alzheimer's Disease Cooperative Study (ADCS), a clinical trial consortium supported by the National Institute on Aging.
The study was a double-blind, placebo-controlled multicenter trial that randomly assigned 390 patients from 45 centers in the United States and Canada to receive 400 mg/kg or 200 mg/kg of IVIG or placebo.
After 18 months of treatment, there was no significant difference in the rate of cognitive decline (measured by using the Alzheimer's Disease Assessment Scale–Cognitive Subscale [ADAS-Cog]) vs placebo or any statistically significant change in functional ability (measured by using the Alzheimer's Disease Cooperative Study–Activities of Daily Living [ADCS-ADL]) vs placebo.
Table. GAP Study: Co-Primary Endpoints
| Endpoint | IVIG, 400 mg/kg | IVIG, 200 mg/kg | Placebo |
| ADAS-Cog | 7.4 | 8.9 | 8.4 |
| ADCS-ADL | –11.4 | –12.4 | –11.4 |
The study was not powered to show statistical significance among the subgroups, the statement notes, but in the prespecified subgroup analysis, the 400 mg/kg treatment group showed a positive, numeric difference in the change from baseline ranging between 16% and 29% vs placebo in cognition on the ADAS-Cog and Modified Mini-Mental State Examination among moderate patients and carriers of the ApoE4 genetic marker. The company has made a data table available.
Treatment was well tolerated, and no new safety signals were identified in this patient population, the company said. IVIG is already used to treat other autoimmune and neurologic disorders. The most common adverse reactions seen in the GAP study in at least 5% of patients were rash and decreases in hemoglobin. The rate of thromboembolic events did not differ in the treated vs placebo groups. Seventeen adverse reactions were considered to be treatment-related in the study: 12 in the combined IVIG groups and 5 in the placebo group.
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Dr. Norman Relkin |
"No approved or investigational medication for Alzheimer's disease has succeeded in a clinical trial of this size and duration. Unfortunately, observations of IG seen in earlier phases of studies of Alzheimer's patients did not translate into a positive outcome in the GAP study," Norman Relkin, MD, PhD, a neurologist from the Weill Cornell Medical College, New York, New York, and GAP principal investigator, said in the Baxter statement. "Analysis of the full study results is still ongoing. I am optimistic that the knowledge we gain from this study will advance efforts to develop effective treatments for Alzheimer's disease."
Phase 2 results, including extension results reported last summer, suggested long-term treatment had a stabilizing effect in patients with AD over time.
On the basis of the phase 3 results, the statement adds, "Baxter will reconsider its current approach for its Alzheimer's program and will determine next steps after full data analyses. The current Baxter studies of IG in mild to moderate Alzheimer's disease will be discontinued."
Full results, including additional analyses and imaging, will be presented at the Alzheimer's Association International Conference, July 13 to 18, 2013, in Boston, Massachusetts.
"The study missed its primary endpoints; however, we remain interested by the prespecified subgroup analyses, particularly among patients with moderate disease and those who carry a genetic risk factor for Alzheimer's disease, 2 patient groups that are in great need of advances in care. A detailed analysis of the results from the GAP study continues, and we look forward to a greater understanding of the full data set," said Ludwig Hantson, PhD, president of Baxter's BioScience business.
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