Posted on May 7, 2013 · Posted in Brain Injury

In yet more disappointing news regarding  a potential Alzheimer’s-disease cure, Baxter International Inc. this week said it will abandon late-stage trials of the drug Gammagard after it didn’t succeed in improving cognitive decline in patients.

The Deerfield, Ill.-based drug maker issued a press release Monday on the results of it Phase III study of Immunoglobulin (IG), which is made from purified human plasma collected from healthy volunteers.

The pharma company said that its clinical study of IG didn’t meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer’s disease.

The immunoglobulin in plasma contains human antibodies that protect the body against infection, offering important immunomodulatory and anti-inflammatory properties that help treat rare immune-related and neurological conditions. IG treatment is administered on an ongoing basis to help patients maintain adequate levels of antibodies.

The Gammaglobulin Alzheimer’s Partnership (GAP) study was conducted by Baxter in collaboration with the Alzheimer’s Disease Cooperative Study (ADCS), a clinical trial consortium supported by the United States National Institute on Aging in the National Institutes of Health.

“Topline analyses from the randomized, double-blind, placebo-controlled, multi-center trial found that after 18 months of treatment, patients with mild to moderate Alzheimer’s disease taking Baxter’s IG treatment at either the 400 mg/kg or the 200 mg/kg dose did not demonstrate a statistically significant difference in the rate of cognitive decline as compared to placebo (mean 7.4 in the 400 mg/kg group, 8.9 in the 200 mg/kg group, and 8.4 in the placebo group),” the press release said.

“Results also did not indicate a statistically significant change in functional ability as compared to placebo (mean -11.4 in the 400 mg/kg group, -12.4 in the 200 mg/kg group, and -11.4 in the placebo group),” according to the press release.

However, in the pre-specified sub-group analysis, the 400mg/kg treatment arm showed a positive, numerical difference in change from baseline versus placebo in cognition as measured by the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and Modified Mini-Mental State (3MS) Examination among both moderate patients and carriers of the ApoE4 genetic marker. These differences ranged between 16 percent and 29 percent.

“The study missed its primary endpoints, however we remain interested by the pre-specified sub-group analyses, particularly among patients with moderate disease and those who carry a genetic risk factor for Alzheimer’s disease, two patient groups that are in great need of advances in care,” said Ludwig Hantson, president of Baxter’s BioScience business.

“A detailed analysis of the results from the GAP study continues, and we look forward to a greater understanding of the full data set,” he said. “We are grateful for the participation of the patients and physicians in the study and for the dedicated support of the patients’ caregivers.”

IG was well-tolerated in the study and no new safety signals were identified associated with treatment in this patient population, ages 50 to 89. The most common adverse reactions (observed in at least 5 percent of patients) during treatment with IG were rash and decreases in hemoglobin.

“Based on these results, Baxter will reconsider its current approach for its Alzheimer’s program and will determine next steps after full data analyses,” the company said.

“The current Baxter studies of IG in mild to moderate Alzheimer’s disease will be discontinued,” the press release said. “Additional analyses from the study, including imaging, will be made available later this year as part of a full presentation of the GAP study at the Alzheimer’s Association International Conference, July 13 to 18 in Boston.

“No approved or investigational medication for Alzheimer’s disease has succeeded in a clinical trial of this size and duration,” Dr. Norman Relkin, a neurologist from the Weill Cornell Medical College and GAP Study Leader, said in a statement.

“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,” he said. “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.”

The GAP study was the largest placebo-controlled study of immunoglobulin, and was designed to assess the safety and effectiveness of Baxter’s IG as a potential treatment for signs and symptoms associated with Alzheimer’s disease.

The clinical trial treated 390 patients with mild to moderate Alzheimer’s disease across 45 centers in the United States and Canada. Patients were randomized to treatment with Baxter’s IG treatment at either 400 mg/kg or 200 mg/kg dosing every two weeks for 18 months, or placebo.

About the Author

Attorney Gordon S. Johnson, Jr.
Past Chair Traumatic Brain Injury Litigation Group, American Association of Justice :: 800-992-9447