By Bill Berkrot and Ransdell Pierson
NEW YORK (Reuters) - After decades of Alzheimer’s research that led to dead ends, including 123 drugs that failed, top researchers in the field say they are far more confident now of producing an effective treatment.
Their optimism has been building ahead of the Alzheimer's Association International Conference (AAIC), which starts on Saturday in Washington, DC. New experimental drugs from Eli Lilly and Co and Biogen have shown promise in slowing down the progression of the mind-wasting disease, attracting the attention of investors and patients.
Those drugs are still very early in their development and could still join the scrap heap. But the field has gained a major understanding of how the brain changes with Alzheimer’s and better insight on how and when to intervene medically.
"The recurring platitude, which has been going on forever is 'gee we're about five years away from a really effective treatment,'" said Steven Ferris, who directs the Alzheimer's clinical trials program at NYU Langone Medical Center in New York.
"It would be premature to say we've turned the corner but there's a lot going on in the pipeline that is quite promising,” said Ferris, who has been involved in trials for over 40 years.
The Lilly and Biogen drugs block beta amyloid, a protein which causes toxic brain plaques considered a hallmark of the progressive brain disease.
Lilly’s solanezumab showed signs of benefiting patients with a mild form of the disease in 2012. In March, Biogen’s aducanumab became the first experimental drug to significantly reduce beta amyloid in the brain and slow impairment in patients with mild disease. Both companies will present new data next week.
"This year is different because multiple mechanisms are being explored and there's a tremendous revival of faith in the anti-amyloid approach," said Dr. Reisa Sperling, director of the Center for Alzheimer's Research at Harvard Medical School.
Sperling's hope is that several drugs that work differently will prove effective and can be used together for "a 1-2-3 punch" to Alzheimer's, as combination treatments now control cancer and heart disease.
An estimated 5 million people have the disease in the United States. The Alzheimer’s Association estimates that as many as 28 million Americans will develop the disease by midcentury and account for 25 percent of U.S. Medicare spending on the elderly in 2040.
PROOF OF BENEFIT
Biogen will present data on a 6 milligram dose of aducanumab on Wednesday, and researchers hope it will provide the right combination of effectiveness, with less of a brain-swelling side effect, than observed with other doses. If the 6 mg dose fails to show a significant improvement over placebo, the result could hurt Biogen shares.
Researchers say they have improved the selection of patients for Alzheimer’s trials, making sure they are not suffering from another form of dementia by checking for beta amyloid, and by testing treatments before the disease becomes too advanced to have an impact.
Biogen Chief Executive George Scangos said that until recently, over one-third of patients referred to trials of its drugs didn’t have Alzheimer’s
“We're at a stage now where we understand the appropriate patient populations,” Scangos said on a conference call with reporters.
Lilly estimates about 25 percent of patients in its previous Phase III trials were likely inappropriate candidates. An ongoing Phase III program will use brain imaging technology to ensure all patients have the amyloid plaque.
On Wednesday, Lilly will present follow-up data from its earlier studies, showing whether those mildly affected patients who continued to take solanezumab for the last two years fared better than those who had initially taken a placebo for 18 months but then switched over to the actual drug.
The Alzheimer’s meeting will also highlight an anti-inflammation drug called azeliragon abandoned years ago by Pfizer Inc when it proved ineffective after 12 months of study.
Pfizer's tiny partner, privately held TransTech Pharma, continued to follow patients who had taken the drug and discovered their cognition had improved after 18 months - the primary goal of the study. The smaller company, which recently changed its name to vTv Therapeutics and aims to soon become public, began a late-stage study of azeliragon in April.
Dr. Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center, agrees with Sperling that a multi-prong approach will be required to keep the disease at bay.
“Another 5 to 8 years down the road, even before symptoms appear, we will be treating with a cocktail of therapies,” he said in an interview.
(Reporting by Bill Berkrot and Ransdell Pierson in New York; Editing by Michele Gershberg and Andrew Hay)