Targeting the $1.33 trillion-worth market of Alzheimer’s Disease (AD), Biogen wants to take a step ahead. Joint with Eisai, the two pharma giants filed a second request of regulatory approval for the new drug, aducanumab, on Oct. 22, 2019, arguing for its effectiveness.
The compound was developed for AD patients, undertaking the hypothesis that the high-level presence of β-amyloid is closely associated with AD development. Researchers synthesized a specialized antibody called aducanumab to minimize the presence of β-amyloid in the nervous system. Debuted for early phase clinical trials in 2011, aducanumab entered its Phase III clinical trials in a larger pool of patients in 2015 . To assess the effectiveness of the compound in clinical trials, a futility analysis was issued to investigate the participants and the overall data collected. The report came up with the conclusion that “the trials were unlikely to meet their primary endpoint upon completion”, which terminated the subsequent trials and further investment.
The capital market reacted positively to the new decision with action: a 40 percent rise of the stock market within one day. When most pharma giants who got frustrated with AD and subsequently shifted their focus to other interests, why did Biogen stick with this mysterious disease with Aducanumab?
One of the reasons may be the ever-growing market for AD and, in contrast, failures of other pharmaceutical companies. Estimated $1.33 trillion in 2020, the US $2.54 trillion in 2030, $4.83 trillion in 2040, and $9.12 trillion in 2050, the market value of AD is immense . Big pharmas are racing to take exclusive advantage of the trillion-value market. However, most of them are facing major failures in both Phase III clinical trials and consequential stock market oscillation. Eli Lilly and Company received a 10.8 percent drop in stock price after solanezumab, a new drug combating AD, testified to fail Phase III clinical trial in 2016, meeting the historically low price in the past three years. In 2018, Johnson & Johnson terminated the Phase III clinical trial for atabecestatll, an inhibitor of Beta-secretase enzyme in the brain . Pfizer decided to “end our neuroscience discovery and early development efforts and re-allocate [spending]” in the same year .
So did Biogen. The pharmaceutical giant terminated Phase III clinical trials for aducanumab this spring based on a futility analysis conducted by an independent data monitoring committee, resulting in a 30 percent drop in their stock price in a single day, which vaporized $18 billion of its values. Though the overall increasing revenue from the last year has made a great financial report in the latest fiscal quarter, the success in multiple sclerosis drug development is not good enough to cover up the termination of aducanumab. Therefore, it is plausible for Biogen to at least try to turn the waste into treasure by digging into the data collected.
As Biogen claimed, the data set used in the futility test was somewhat incorrectly arranged and incomplete. From March to September, they were able to record the latest clinical results during the six-month extended period and replenish their database. Originally, their data was distributed based on the clinical trial program into two major collectives: participants who took generally larger doses and had longer exposure to aducanumab (“Engage”) and the participants who did not (“Emerge”). They then found a subset group within the Engage group that’s actively responsive to the treatment. With these specifications, Biogen statistically proved the effectiveness of aducanumab for AD treatment given certain doses . However, the question lies exactly in the validity of their reasserted data analysis.
Would the result remain applicable to a larger gene pool? It is clear that Biogen strictly rearranged the data to support its claim with a limited number of participants. When it comes to Phase IV clinical trials or even actual clinical applications, can aducanumab overcome the diversity of genes and do a great job with patients globally?
The validity of the β-amyloid hypothesis is worrisome as well. With countless money (in a literal sense, countless) being spent on drugs reducing β-amyloid presence in the brain, no success was ever made. Could researchers attribute recent clinical trial failures to the hypothesis itself? Maybe the accumulation of β-amyloid is produced to cope with the damage instead of being the damage itself .
There is no settled answer to any question about Alzheimer’s disease.. With 113 years of research, no one knows exactly about it. What protein, virus, or bacteria is responsible for AD? How does genetic background affect one’ s chances of getting AD? To some extent, there are so many mysteries in AD that it is more of a mystery than a medical condition. In the mist of finding cures for AD patients, Biogen is taking a cautious but forward leap.
Edited by: Anhthi Luong
Illustrated by: Jennifer Broza