In an unexpected reversal, pharmaceutical giant Biogen said it will pursue US Food and Drug Administration approval for aducanumab, an experimental treatment for early Alzheimer's disease, Biogen and its Japanese partner Eisai announced on Tuesday.
Phase 3 clinical studies of aducanumab were discontinued in March. The trials were halted because results of a futility analysis found they were unlikely to meet their primary goals at completion.
On Tuesday, Biogen announced that a new analysis, which included more patients, showed a significant reduction in clinical decline in one trial. Results for some patients in another study support those findings, as well.
The data showed that patients who received aducanumab experienced significant benefits on measures of cognition and function, including memory, orientation and language, according to Biogen.
"I really hope these new analyses pan out," said Dr. Richard Isaacson, director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine in New York, who had patients in the original clinical studies.
"I'm not surprised that a reanalysis of the data showed something positive," he said, adding, "I do believe that there are going to be probably continued regulatory hurdles."
Additionally, the drug could be extremely expensive, Isaacson said.
"The complicated aspect here is I would not be surprised if additional analyses, with larger (numbers), with higher doses, do show signals in either the overall population or subgroup analysis, but is that going to be enough for the FDA to approve this from a regulatory perspective? Would payers reimburse it? I don't know, but I hope so," he said.
'We are hopeful'
The company Biogen said it will file an application with the FDA in early 2020 and will continue discussions with regulatory authorities in Europe and Japan. It will also offer access to aducanumab to eligible patients previously enrolled in the phase 3 studies.
"This is the result of groundbreaking research and is a testament to Biogen's steadfast determination to follow the science and do the right thing for patients," Biogen CEO Michel Vounatsos said in the company's announcement on Tuesday.
"We are hopeful about the prospect of offering patients the first therapy to reduce the clinical decline of Alzheimer's disease and the potential implication of these results for similar approaches targeting amyloid beta," he said.
The "amyloid hypothesis" says it's the accumulation of beta-amyloid in the brain that is the primary cause of the memory-destroying disease. The hypothesis has been the driving force behind Alzheimer's research for more than 20 years.
Yet most attempts to develop amyloid-targeting drugs in people with the disease have failed.
In late 2016, Eli Lilly's solanezumab failed to surpass placebo benefits in a Phase 3 trial of 2,100 patients. In 2013, Pfizer scrapped another antibody, bapineuzumab, when it didn't surpass placebo effects in another Phase 3 trial. Experts suggest that the advanced stages of Alzheimer's among study participants in both trials might have contributed to the failures.
Merck used a different approach to fight beta-amyloid in people with late-stage Alzheimer's with its BACE inhibitor verubecestat but admitted defeat in early 2017 after an independent study found that it had "virtually no chance" of working. A second attempt to treat earlier stages of Alzehimer's was also scrapped in February.
Johnson & Johnson's BACE inhibitor atabecestat, designed to slow cognitive decline in people at risk for Alzheimer's, was also scrapped in May 2018 when liver enzymes spiked in study participants.
Waiting in anticipation
Alzheimer's disease is the sixth leading cause of death in the United States. About 5.8 million people in the United States currently live with Alzheimer's, and that's projected to rise to nearly 14 million by 2050.
The Alzheimer's Association applauded Biogen for pursuing regulatory approval for aducanumab.
"The Alzheimer's Association is encouraged to learn that Biogen will pursue regulatory approval from the FDA for the investigational drug aducanumab based on Phase 3 clinical trial results from the EMERGE and ENGAGE studies, and other related data, after finding a reduction of cognitive and functional decline in people taking the high dose," Maria Carrillo, chief science officer at the Alzheimer's Association, said in a written statement on Tuesday.
"We eagerly anticipate reviewing a full report of findings referenced in today's Biogen announcement."