SNHS Biology Blog 9: To Emerge or to Engage

Sonal Churiwal

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Don’t judge a book by its cover. I learnt it by wasting my money on a really bad book just because it came with a free necklace at the third grade book fair, but Biogen learnt it the hard way. While analyzing the results of two separate studies, EMERGE and ENGAGE, of the drug aducanumab to erode amyloid plaques associated with Alzheimer’s, Biogen mistakenly halted clinical trials of the miracle drug that is now being submitted to the FDA for approval. Both the trials were structurally very similar; however, ENGAGE began enrollment one month prior to EMERGE in 2015. As every good event is followed by an unfortunate one, a major side effect of aducanumab can be AIRA, or brain swelling. When reviewing ways to administer the drug to decrease chances of brain swelling, researchers decided to gradually increase the dosage, leading to two trial modifications in March 2017.

Because of the potentially fatal risks of this, patients with higher risks to experience AIRA were initially prescribed a lower dosage than other patients. However, the first change modified this to allow these patients to resume the drug at their original dose and gradually reach a higher dosage, suspending the drug at any point of time in case of AIRA. The second modification was to actually increase the maximum dosage of the drug to be administered.

In both trials, the patient could receive no more than 14 doses; because EMERGE started after ENGAGE, the patients had more blank spaces left for the higher dosage and led to results different than ENGAGE. Only 15% of patients in ENGAGE received the maximum dosage as opposed to 22% in EMERGE; therefore, ENGAGE received results that were not as promising. Furthermore, ENGAGE had a larger sample size than EMERGE, so when both studies were combined for a holistic analysis, the negative results were overshadowing the promising results, bringing the trial to a halt. Later on, upon further analysis and investigation into the trial, the reason for the skewed results was uncovered and aducanumab was revealed to actually be able to reduce the progression of Alzheimer’s. Although this drug seems to be the solution to a devastating mental illness facing millions, the logistics of it are yet to be investigated. The cost of this drug is still unknown, as well as whether or not healthcare insurance providers are willing to cover the cost of the drug. For many, the reversal rates of Alzheimer’s may seem marginal and not worthy of such time at a 22% reduction, but for those seeing their loved ones slowly disappear, this drug has become a shining beacon of hope.

Ultimately, the development and approval of this possibly miracle drug was undeniably delayed because of the lack to look beyond what is seen. This trial proves the immense effort and meticulous analysis that is necessary to go into every research project in order for its end result to be successful and conclusive.