On Monday, June 7th 2021, the U.S. Food and Drug Administration (FDA) approved the first new drug for Alzheimer’s disease in 18 years. The new drug, Aduhelm, (known formally as aducanumab) was developed by the Cambridge, MA, biotech company Biogen, and is the first Alzheimer’s drug aimed at targeting a possible cause of the disease—the accumulation of misfolded protein in the brain known to be a disease hallmark—rather than just manage symptoms.
Despite what seems like news that would garner universal celebration, the FDA approval has generated fierce debate. This is largely due to the nature of the approval under the Accelerated Approval Pathway. This route is taken when the FDA believes a drug is capable of providing meaningful therapeutic benefit over existing treatments, despite remaining uncertainties regarding its efficacy in the clinic. Some in clinical research worry that the data reported from the Phase III Aduhelm trials does not provide clear evidence that the new treatment helps patients, and fear the drug may have potentially serious side effects.
Further complicating decisions regarding Aduhelm approval is the drug's proposed price. Biogen has stated that it plans to offer the drug at a cost of $56,000 per patient per year. Whether or not this price represents a fair price based on the expected value the drug will bring to patients, caregivers, and society is uncertain.
With millions of Americans affected by Alzheimer’s it is important for our current patients, the future of health economics, and the future of clinical trials that the proper course of action is taken. Given the importance of deliberations regarding the convoluted Aduhelm approval and its current relevance in the biotech industry, clinical research, and society in general, the case serves as a valuable study of the ethical considerations involved in clinical research and new drug approval. In this blog post, I will analyze some of the ethical dilemmas that arise in clinical research through the lens of the Aduhelm approval case. I will ultimately offer an opinion on whether or not the FDA’s accelerated approval of the drug was ethically justifiable.
Informed Consent in Clinical Trials
Informed consent can be complicated in any clinical setting. During clinical trials specifically, additional complications can arise due to the uncertainty of treatment outcomes. Given that the treatment being offered is exploratory in nature, it is difficult to achieve true informed patient consent as there may be limited existing data to support whether or not the proposed treatment will have any clinical benefit.
Adding to the complexity of obtaining informed consent in clinical trials is the patient’s state of being. Many enrolled in clinical trials are incredibly ill individuals who have exhausted all other forms of treatment available. Cognitive decline and mental despair may accompany their poor health and interfere with extremely sick or terminally ill patients' ability to make rational decisions. Furthermore, pressure from friends or family members who are also impacted by the desperate situation may add to the difficulty.
In the case of Aduhelm, obtaining informed consent in clinical trial patients is fraught with the complications mentioned above. The accelerated approval by the FDA and remaining uncertainty regarding the drug’s efficacy make it difficult for patients to gain a complete grasp on the outcomes of the recently approved treatment. Moreover, the devastating cognitive decline experienced by those with Alzheimer’s disease can make it incredibly challenging to obtain true and rationally decided decisions regarding their treatment. In order to overcome these barriers, it is essential for new drugs advancing through clinical trials to have well-proven efficacy and safety.
Challenge of Equitable Drug Pricing
Drug pricing in the biotech and biopharmaceutical industry is challenging because of the multiple stakeholders involved in decision making. Companies may face conflicting duties to patients—who need the developed products at accessible prices—and investors—who are owed financial benefit for their support of the company and their role in developing products. Further, while the ultimate goal of a company is to provide new solutions for those with unmet medical needs, the significant cost of research and development may prevent them from offering new drug products to patients at affordable costs.
Looking at the case of Aduhelm, working towards equitable drug pricing is challenging. From the perspective of Biogen, which spent billions of dollars and countless hours in the development of this new drug, offering it at the steep cost of $56,000 per year per patient may be necessary in order to recoup losses from research and development. From the perspective of patients however, the cost of treatment has the potential to place on them an incredible financial burden, or simply to be out of reach. This is especially true when one considers the additional patient costs associated with monitoring potential side effects, which could reach up to $30,000 a year.
More broadly, this case and the topic of equitable drug pricing raises greater concerns regarding healthcare accessibility and justice. While those from upper income levels may have the means to afford Aduhelm, those with lower incomes may not have the opportunity to potentially slow or stop the spread of their progressive cognitive decline. Furthermore, the average American, whose tax dollars may be spent to subsidize the ability of low-income individuals to receive these extremely expensive treatments, may face significant financial burden. To begin addressing the plethora of concerns and unknowns regarding Aduhelm pricing, it is crucial for both Biogen and policymakers to be transparent with their deliberations in determining costs.
Is the Accelerated Approval of Aduhelm Ethical?
The overall question this blog seeks to answer is whether or not the accelerated approval of Aduhelm by the FDA was ethically justifiable. From an ethical standpoint, it is important to weigh the risks and benefits involved in the decision to approve the new drug. In regards to its benefits, the drug has incredible potential to improve the quality of life for the millions of individuals who suffer from the devastating effects of Alzheimer’s disease. Further, its approval may pave the way for the success of future accelerated approval pathways that will provide faster solutions to those with unmet medical needs. Looking at the potential risks, there is still some uncertainty in the overall efficacy of the drug given the rapid pace of its approval. These unknowns can potentially infringe upon the consent given by clinical-trial patients. Additionally, the high cost of the drug could further exacerbate existing inequities in the U.S. healthcare system.
For a final consideration in my analysis of this case, I would like to take into account the dialogue and debate that has accompanied it. The FDA’s accelerated approval of Aduhelm immediately generated conflict between the various stakeholders involved. Notably, both the FDA’s independent advisory committee and the American Geriatrics Society were against the approval of the novel drug, with concerns regarding the drug's efficacy. These conflicts may be interfering with the fair and safe production of treatment for patients. In order for the best possible outcome for patients with Alzheimer’s—the number one priority in this decision—dialogue should be taking place rather than conflict.
Based on these deliberations, I do not believe the accelerated approval of Aduhelm is ethically justified. A safer and more positive outcome for Alzheimer’s patients can be achieved by ensuring efficacy in phase III clinical trials before moving forward. Doing so will also allow time for stakeholders to work together to find solutions towards equitable drug-pricing issues and best protect the rights of patients.