Biogen Inc. will file its previously scrapped Alzheimer's disease drug, aducanumab, for U.S. Food and Drug Administration approval, stunning investors and analysts who believed the experimental therapy was gone for good.
Biogen and its Japan-based partner Eisai Co. Ltd. halted two late-stage trials for aducanumab in March after futility analyses suggested the studies would not meet their goals. But a newly released analysis of a larger set of patients from the phase 3 trials, called Emerge and Engage, showed that aducanumab actually met its main goal of reducing clinical decline in the Emerge trial, according to Biogen's Oct. 22 press release.
The companies plan to file the application for the U.S. regulator in early 2020.
Leerink analyst Geoffrey Porges wondered whether the news is "the dawn of a new era or a relapse in amyloid addiction" for Biogen, one of the few remaining large biotech companies in the Alzheimer's space.
Aducanumab targets the amyloid plaques that form in the brain in Alzheimer's, based on the theory that reducing the protein tangles and plaques will slow the disease's effects on memory and function. Multiple drug candidates by the likes of Eli Lilly and Co. and Roche Holding AG working off of this hypothesis have failed and been discontinued prior to Biogen's March announcement to abandon aducanumab.
Analysts therefore had labeled aducanumab's apparent failure the final nail in the amyloid theory coffin.
"The result of the futility analysis was incorrect," Biogen said in its data update presentation.
The Cambridge, Mass.-based company's stock was trading up approximately 36.9% to $305.88 as of 9:45 a.m. ET on Oct. 22. Eisai's stock also jumped about 46.1% to $75 as of 9:34 a.m. ET.
The update was based on an analysis of 3,285 patients with mild cognitive impairment due to Alzheimer's disease, compared to the previously presented population of 1,748 patients. Out of the 3,285 patients across Emerge and Engage, 2,066 completed the full, planned 18 months of treatment with aducanumab. The identically designed trials included patients treated with a placebo drug, a lower dose of aducanumab and a higher 10-milligram dose of aducanumab.
In Emerge, patients treated with the higher dose of aducanumab achieved a 23% reduction in clinical decline versus placebo at 78 weeks. The high-dose-treated patients also met the secondary goals of the Emerge trial, demonstrating a consistent reduction in clinical decline, including mental state, cognition and daily function. In both the low dose and high dose groups of the trial, patients experienced a reduction in amyloid plaque compared to placebo at 26 and 78 weeks.
Biogen said the difference between the previous futility analysis and the larger data set results was the higher dose of aducanumab. Patients on the lower dose of the drug did not meet the Emerge trial's goal of reducing clinical decline, though they did see a 14% to 16% reduction.
The Engage trial still did not meet its goals of reducing clinical decline, but Biogen said the high dose patient group again demonstrated some reduction in clinical decline, supporting the Emerge trial's results.
"Exposure to high dose aducanumab was important for efficacy," Biogen concluded.
The safety data was similar to previous aducanumab studies, with headache and swelling being the most common side effects.
Evercore analyst Umer Raffat noted some inconsistencies in the presented efficacy data: "in totality, the low dose looks more consistent than the high dose" in terms of clinical decline reduction, he said. The patients who did not complete the full length of aducanumab treatment appeared to still show supportive effects in reduced disease-related declines, Raffat added.
"This is confusing," Raffat wrote, following Biogen's data presentation.
Nevertheless, both Raffat and Leerink's Porges said Biogen has discussed the data with the FDA.
"Given the unmet need and the signal seen in high dose Emerge, it's not inconceivable that FDA is open to this filing," Raffat said. "However, whether FDA approval means major commercial acceptance is a whole different debate."
Porges said the FDA discussions could possibly suggest a guaranteed approval.
"Regardless, this filing will come down to a torturous discussion of data, statistics, endpoints, exposure, treatment effects and safety liabilities," Porges wrote.
Biogen reported third-quarter earnings as the aducanumab news was released, with the surprise filing dominating discussion on the Oct. 22 conference call.