US-based biotechnology firm Biogen on Tuesday announced that it will seek regulatory approval from the US Food and Drug Administration (FDA) for its drug ‘aducanumab’, which is an investigational treatment for early Alzheimer’s disease (AD). A new analysis called “EMERGE” led by the company in consultation with the FDA shows that administration of the drug may be able to reduce clinical decline in patients in the early stages of AD. If approved by the FDA, aducanumab will become the first therapy to reduce clinical decline in patients.
“Patients also experienced benefits on activities of daily living including conducting personal finances, performing household chores such as cleaning, shopping, and doing laundry, and independently traveling out of the home,” according to a press release issued by Biogen.
According to US-based Alzheimer’s Association, AD affects over 4 million people in India. Until now, no cure or a method to stop the progression of the disease exists.
What is AD?
AD is a progressive brain disorder that affects older people, leading to loss of memory, decline in functional ability and change in personality and behaviour. Early onset AD, on the other hand, can affect individuals younger than 65 years of age. An individual affected by the disease may eventually be unable to perform everyday tasks. While AD is a disease, dementia is the name given to the symptoms of AD. Furthermore, AD is considered to be the most common cause of dementia, which can be caused by Huntington’s and Parkinson’s disease as well.
In April 2011, new guidelines and criteria for diagnosis of AD were published. According to these criteria, there are three stages of the disease. The first is the preclinical stage, which may last for ten years or more and is marked by evidence of abnormal biomarker (biomarkers measure the severity of disease) patterns. In the second stage, some symptoms of AD, such as cognitive impairment can be noticed and the third stage is the complete manifestation of the disease.
Early stage of AD is not the same as early onset AD, which is diagnosed in patients younger than 65 years of age. Aducanumab is meant to be effective for the patients in the former category.
Why has it been so difficult for scientists to come up with a cure for Alzheimer’s?
The last time a drug was approved by the FDA was in 2003, this is primarily because the exact causes of the disease are not known, making drug discovery for AD a challenging task. Even so, there is some consensus in the scientific community that the disease involves two proteins – beta amyloids and tau. When levels of beta amyloids reach abnormal levels in the brain, it leads to the formation of plaque, which gets deposited between neurons damaging and disrupting nerve cells. But it is not known why the levels of these proteins reach abnormal levels in the first place.
Most AD drugs try to target these proteins in order to manage some of the symptoms of the disease. According to the Alzheimer’s Association, there exist five FDA approved prescription medications to treat the symptoms of AD, while some of these can be used for all stages of the disease, some are meant for particular stages of it. Three among these medicines are “cholinesterase inhibitors”, that prevent chemical messengers in the brain from breaking down, messengers that help in learning and memory. But no drug exists as of now that can slow down the progression of the disease, let alone cure it.
The study and the drug
In the case of aducanumab, two studies called EMERGE and ENGAGE were conducted by Biogen that enrolled 1,638 and 1,647 patients, respectively. These two studies were designed to evaluate the efficacy and safety of two dosing regimens of aducanumab in patients with AD in the early stages.
The two trials were discontinued in March 2019 after the smaller set of data showed that the drug would not be effective. After discontinuation of these two studies, additional data became available and after fresh analysis it was concluded that patients who received higher doses showed a slower cognitive decline, signalling that the results of EMERGE were statistically significant. Furthermore, Biogen believes that a subset of data from ENGAGE also confirms the results of EMERGE, even though ENGAGE itself was not successful study.
Like many other AD drugs, aducanumab works by targeting the protein beta amyloid, which means it tries to clear its deposits. “This large dataset represents the first time a Phase 3 study has demonstrated that clearance of aggregated amyloid beta can reduce the clinical decline of Alzheimer’s disease, providing new hope for the medical community, the patients, and their families,” said the trial’s principal investigator Dr Anton Porsteinsson.
Even so, it should be noted that the trial focussed on patients with AD still in the early stages, when the damage to the brain is relatively less than the advanced stages. Furthermore, the findings of the trial have not yet been published in peer-reviewed journals.