A new study published in the journal JAMA Neurology is reporting more than one in three patients trialing the recently approved Alzheimer’s drug aducanumab experienced brain swelling side effects. The data is the first from the controversial drug’s Phase 3 trials to be peer-reviewed and published.

In June the US Food and Drug Administration (FDA) approved the first new drug treatment for Alzheimer’s disease in almost 20 years. Aducanumab (also known as Aduhelm) traversed a rocky path to market approval after its large Phase 3 trials were initially discontinued due to early indications it didn’t work

A subsequent analysis of the trial data by Biogen, the company developing the drug, revealed the earlier conclusions may have been premature and the drug did actually show positive efficacy in some conditions. This ultimately led to a controversial FDA approval that went against the advice of its own independent advisory panel.

Now, several months later, the aducanumab story continues as a secondary analysis of the trial data reveals 41.3 percent of all trial participants experienced some kind of brain imaging abnormality over the course of the study. The side effects have been dubbed amyloid-related imaging abnormalities (ARIA) and manifest as either brain swelling (ARIA-E) or brain hemorrhages (ARIA-H).

The study reports 35.2 percent of participants in the trial on the highest dose of aducanumab (the dose approved by the FDA) showed some degree of brain swelling on MRI scans. Brain bleeding was detected in 19.1 percent of participants on the highest dose.

The report indicates the majority of those ARIA cases were asymptomatic and transient, with only 1.4 percent of cases deemed serious. No deaths were reported in the trial from these side effects.

This newly published safety data arrives in the wake of recent news revealing the death of a 75-year-old woman in Canada. The woman, participating in an ongoing long-term aducanumab trial, was diagnosed with brain swelling and bleeding.

An independent physician investigating the woman’s case concluded the death was “likely” related to aducanumab. However, a statement from Biogen argues the cause of death is still unknown at this stage and an investigation is underway.

“We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure and diagnosed with cerebral edema thought to be ARIA-E,” Biogen’s recent statement reads. “Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility. We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.”

In a further blow to the fortunes of aducanumab an advisory panel to the European Medicines Agency (EMA) recently issued what is called a “negative trend vote” after reviewing the drug. This precedes the panel’s upcoming formal recommendation regarding whether the EMA should approve the drug for use in Europe. This panel decision is thought to strongly foreshadow an EMA rejection of the drug.

The new data was published in the journal JAMA Neurology.