A 6 mg dose of Biogen's experimental Alzheimer's disease drug significantly reduced beta amyloid plaque in the brain but failed to significantly slow mental decline, potentially tempering great enthusiasm that greeted data on two other doses of the treatment earlier this year.

The 6 mg data, which showed some slowing of mental decline, were presented on Wednesday at the Alzheimer's Association International Conference (AAIC) in Washington, D.C.

The biotech drug, aducanumab, was hailed as a potential breakthrough in March when it became the first Alzheimer's treatment to significantly slow cognitive decline and reduce what is believed to be the brain-destroying plaque in patients with early and mild forms of the disease, according to 54-week data from a small, early stage trial.

The surprisingly positive results were seen at doses of 3 mg/kg of weight and 10 mg/kg, and they were more pronounced at the higher dose. A 1 mg dose was not much better than placebo.

The results also revived the theory of amyloid plaque as a leading suspect in causing the debilitating effects of the disease, an approach used by other drugs as well, such as Eli Lilly's solanezumab.

Investors and the Alzheimer's community had hoped 54-week data for the 6 mg dose of aducanumab would slip nicely between the 3 and 10 mg results, confirming what was seen earlier. But it fell short on one of the more critical measures for patients.

Biogen said statistical significance in a small Phase I trial was less important than the positive effect of the overall results, calling them "absolutely encouraging."

"I'm very pleased with the result," said Jeff Sevigny, Biogen's medical director for clinical development, who presented the data. "The 6 mg/kg dose fit in quite nicely on one measure (plaque reduction), and on another measure it came within the ballpark."

In addition to plaque removal, the trial used two measures to test cognition: a questionnaire with a 30-point scale to test mental acuity and an 18-point Clinical Dementia Rating scale that tests mental decline and loss of ability to function.

On the first measure, 6 mg patients worsened by 1.96 points, which was numerically better than placebo and 1 mg, but short of the significantly slower declines seen with the other doses.

On the second measure, which will be used in confirmatory trials, only the highest dose achieved statistical significance, but the decline seen with 6 mg fell between 3 mg and 10 mg.

The drug was well tolerated, Biogen said.

SIDE EFFECT HAD NO SYMPTOMS

Researchers found a similar dose dependent incidence of buildup of fluid around the brain, known as ARIA-E (amyloid-related imaging abnormalities-edema), as had been observed earlier. The rate was higher among those with a gene associated with the highest risk for developing Alzheimer's.

That side effect was seen primarily during the early part of treatment, had no symptoms, and resolved generally in four to 12 weeks, Sevigny said.

The trial involved 166 patients with only about 30 in each dosing arm. Biogen has begun screening for Phase III trials to include about 2,700 patients, which should determine the true value of aducanumab. Results of those studies, if successful, would be used to seek approval of the drug.

Alzheimer's affects 15 million people worldwide, a number that is expected to grow to 75 million by 2030 without effective treatments. Any effective treatment is sure to become one of the world's most lucrative drugs.