Mixed bag? Biogen's aducanumab shows continued dose-correlation
This article was originally published in Scrip
Biogen reported data from the 6mg/kg cohort of its PRIME trial of aducanumab at the Alzheimer's Association International Conference (AAIC) on 22 July that will likely leave investors itching for more clarity. The data continue to show dose correlation in efficacy, but safety issues persist at the mid-range dose as well.
While the early stage trial was just meant to test safety and tolerability, secondary endpoints include change from baseline at 26 weeks of beta-amyloid plaque and cognitive functioning, as well as those outcomes as the end of 54 weeks of treatment. Mental impairment in patients was measured using the Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales, while beta amyloid plaque deposits were measured using PET imaging with the radiotracer florbetapir. Scans were conducted at baseline, 26 weeks and 54 weeks.
The 6 mg/kg results announced at AAIC for aducanumab (previously known as BIIB037) showed that the drug reduced beta-amyloid plaque build up in the brain, but concerns about a dose-dependent adverse event continue. The drug performed as expected, with the 6mg/kg cohort showing results in between previously announced results from the 3mg/kg arm and the 10mg/kg group.
The drug showed manageable levels of safety and tolerability, but aducanumab also showed a dose-dependent, apolipoprotein E4-(ApoE4) status-dependent adverse event of amyloid-related imaging abnormalities-edema (ARIA-E).
Patients given the 10mg/kg dose of the drug and who were also carriers of the gene were more likely to develop the condition that resulted in swelling around areas of the brain. The issue caused a higher incidence of patients on the drug to drop out of the trial. Biogen introduced the intermediate dose of 6mg/kg to the trial after it became evident that the issue was dose-dependent.
ARIA-E developed in about 33% of the patients in the 6mg/kg cohort, compared with 47% of patients in the higher dose and only 5% of patients on placebo.
Major market potential
Biogen announced the results from the 1mg/kg, 3mg/kg and 10mg/kg dose cohorts at 54 weeks from the Phase Ib study in March. The results were positive and were the first time that a drug showed potentially disease-modifying attributes, reducing the amount of plaque in patients' brains, as well as improving cognitive function.
While plaque levels were virtually unchanged at both measurements in placebo patients, there was a statistically significant reduction in plaque at 26 weeks in all treatment arms.
Biogen's Alzheimer's disease drug aducanumab has been drawing plenty of investor interest over the last year as people have speculated that the early stage drug could be a blockbuster. The positive results from March prompted the company to initiate a large Phase III trial that is expected to begin later this year.
The theory that accumulation of beta-amyloid plaque in the brain causes the disease has long been batted around in the field, but, until now, no drug has been able to show a statistically meaningful reduction in the plaque while also improving the cognitive symptoms that accompany the memory-shattering disease.
Alzheimer's disease has been a particularly tricky development area for big pharma and research has been marked by a slew of late-stage, high-profile failures that have prompted many companies to pull out of the space.
Yet, the growing number of aging baby boomers means that this is a huge market with plenty of unmet need.
Analysts have said previously that they don't believe the results at AAIC are particularly important to the success of the drug, but are keeping a close eye on development and looking for dose titration data in 2016.