Rocky start for Biogen’s Alzheimer’s drug Aduhelm

Embattled Biogen has encountered yet more setbacks in the roll-out of its Alzheimer’s disease monoclonal antibody Aduhelm (aducanumab) in the United States.

Aduhelm’s approval was so controversial earlier this summer that three members of the FDA’s advisory committee resigned when their near-unanimous decision not to recommend the drug was ignored. The price tag of $56,000 has also been heavily criticised.

It has been reported that the roll-out has been far slower than expected with only around 100 patients receiving the infusion in total. Many clinics have announced that they would not be using Aduhelm, including the Cleveland Clinic and Mount Sinai, with one Washington-DC-based clinic taking the worrying step of banning Biogen reps from the premises.

More attention is also being paid to Aduhelm’s side effects, specially ARIA – amyloid-related imaging abnormalities. The most common form is ARIA-E, a type of cerebral oedema that is associated with headache, confusion, nausea and gait disturbances, among other symptoms.

ARIA-E was a common side effect in Aduhelm’s main clinical trials. In the EMERGE and ENGAGE trials – the phase 3 trials that provided the data for Aduhelm’s approval – more than one-third of patients on the approved dose developed ARIA-E, making it the most common adverse event.

However, according to Biogen, 98% of ARIA-E cases resolved on MRI during the studies, with 76% of cases being asymptomatic. Until the company releases the more detailed data necessary to demonstrate that ARIA does not pose a long-term threat, concerns over ARIA will linger.

Biogen’s approval is based on surrogate endpoints but it could be as long as nine years before trials are able to convincingly show that Aduhelm improves cognition. Yet, experts also warn that, while there is no evidence that resolved ARIA has long-term harmful consequences, it cannot be ruled out.

The ongoing controversy around Aduhelm has not helped Biogen’s share price, which after another 2% drop last week has now lost all its gains from a post-approval peak in June.

Analysts are now predicting that Biogen may need to slash the price of Aduhelm.

In a note to clients last week, analysts from Baird revealed that the FDA’s Adverse Event Reporting System (FAERS) showed three reported cases of ARIA between June and August, all of which required hospitalisation. One case was described as life-threatening in the agency’s database.

“We think these additional events reflect a picture of a drug that is far from benign,” said the Baird analysts.