Trial Drug Shows Hints of Efficacy in Alzheimer's

PHILADELPHIA — Alzhemed, an investigational drug believed to prevent formation of amyloid fibrils in Alzheimer's patients, was safe and showed hints of efficacy in a phase II study, Paul A. Aisen, M.D., said at the Ninth International Conference on Alzheimer's Disease and Related Disorders.

The results were encouraging enough to warrant the launch of a phase III efficacy study in 950 patients with Alzheimer's disease, said Dr. Aisen, director of the memory disorders program at Georgetown University, Washington.

In the open-label phase of the current study, in which patients were treated for as long as 20 months, the results were “consistent with a stabilization effect on cognitive function, particularly in patients with mild Alzheimer's disease,” he said at the conference, presented by the Alzheimer's Association.

The study was sponsored by Neurochem Inc., the manufacturer of Alzhemed. Alzhemed is a small molecule that is administered orally and binds to soluble β-amyloid and thereby prevents it from forming amyloid fibrils.

Deposition of amyloid fibrils in the brain is a hallmark of Alzheimer's disease.

The study enrolled 58 patients with mild to moderate Alzheimer's disease. Their average age was about 75 years old, and their average score on the Mini-Mental State Examination was about 20. Patients could be enrolled if they were already on stable treatment with an acetylcholinesterase inhibitor, and about 70% of the patients fell in this category, said Dr. Aisen, who is on Neurochem's clinical advisory board.

Patients were randomized to receive placebo or 50 mg, 100 mg, or 150 mg of Alzhemed b.i.d. The study was designed to continue blinded treatment for 12 weeks, and 52 patients completed this phase. Four of the six dropouts were from the Alzhemed groups, and three of these patients dropped out because of adverse effects (two because of nausea and one due to weakness and weight loss).

After 12 weeks of treatment, the patients who received 100 mg or 150 mg of the drug b.i.d. had a significant drop in the level of β-amyloid in their cerebral spinal fluid, a surrogate marker for what might have happened to the β-amyloid in their brains, Dr. Aisen said.

Patients treated with placebo or the lowest dosage of Alzhemed had no measurable change in their β-amyloid levels. No patients in the study showed a measurable change in cognition during this relatively brief period.

Forty-two of the 52 patients who finished the blinded phase agreed to participate in an open-label treatment phase in which all patients received 150 mg b.i.d. Of the 16 patients who eventually stopped their treatment, two did so as a result of adverse effects, with one patient stopping because of nausea and vomiting and the other because of agitation and delusion.

Among the 19 patients who completed 20 months of treatment, their Alzheimer's Disease Assessment Scale cognitive score rose by an average of 6.2 points (the higher a patient's score, the worse the dementia), compared with an average rise of 11.9 points in historic controls, Dr. Aisen said.

Of the 10 patients from this group who entered the study with mild disease, the average rise in their score from baseline was 2.4 points, compared with an average 8.6-point rise among historic controls.

Formation of amyloid fibril is aggressive in this incubated in vitro model.

After administration of Alzhemed, the amyloid fibril formation is inhibited. Neurochem Inc.