Experts explain: What the FDA’s approval of a new Alzheimer’s drug means for healthcare

In 2019, Alzheimer’s disease was the seventh biggest cause of death globally, so it’s likely you know someone who has been affected. It’s the leading cause of death in the UK, where, of the COVID-19 deaths in March to April 2020, 1 in 5 were people with dementia.

While there are treatments for many of the other main causes of death worldwide, there’s not been an effective therapy to slow the gradual destruction of memory and thinking skills Alzheimer’s causes.

So the announcement on 7 June that the United States Food & Drug Administration (FDA) had granted accelerated approval to the first new treatment for Alzheimer’s in almost 20 years was considered a breakthrough, particularly as cases are rising as the global population ages.

Symptoms usually appear when people are in their mid-sixties – and by 2050, 1 in 6 people will be aged over 65. It also affects women disproportionately, with women making up 65% of those who die from Alzheimer’s and other forms of dementia, according to the World Health Organization (WHO).

While the ‘accelerated approval’ of Biogen’s Aduhelm (aducanumab) infusion has divided the scientific community over its effectiveness, based on the data gathered so far, shares of US-based biotech firm Biogen and its Japanese drugmaker partner Eisai soared.

It’s not a magic bullet, with more research needed on whether it slows the decline in cognition, and it’s also expensive – at $56,000 for a yearly course.

Dr Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, told Reuters the accelerated approval pathway “allows for there being some residual uncertainty on the drug’s clinical benefits while making the drug available to patients rather than having to wait”.

Last year, the World Economic Forum launched the Davos Alzheimer’s Collaborative (DAC), a first-of-its-kind global effort to speed up progress on the discovery, testing and delivery of precision interventions for Alzheimer’s by creating a global innovation ecosystem.

Here, Forum experts, Elissa Prichep and Kelly McCain, from Shaping the Future of Health and Healthcare, explain why the new Alzheimer’s drug is significant and how the FDA approval process works.

Why is it so important to find a treatment for Alzheimer’s?

McCain: Alzheimer’s is a looming global health crisis. It's one we know is fast approaching and devastating to both economies and families, with 60% of the global Alzheimer's and dementia burden in low and middle-income countries. In those countries, it not only impacts the person with the disease, it impacts their entire family structure, because you have much more of a society of caregiving, especially for women that oftentimes will have to leave the workforce to care for these individuals. Currently, the global cost of Alzheimer's and dementia is about $1 trillion.

Nearly 90% of the world's population that suffers from Alzheimer's and dementia is yet to be engaged with current screening and care practices that may help spot signs or risk factors of Alzheimer’s and dementia early, and course-correct. So, when you think about what is the actual global burden and what needs to be solved, [the Biogen drug] is a massive lift. But while this is a massive scientific discovery, there's still so much work to be done. If you think about diabetes or cancer, if you get it early, outcomes are good. But for Alzheimer's and dementia, which is one of the top 10 causes of death worldwide, it's the only one that cannot be prevented, slowed or cured. It's a slow, demoralizing, economically draining death.

What are the R&D phases that new drugs go through before reaching the market?

Prichep: When a product in research shows enough promise to have an impact on a disease, the sponsor will submit an Investigational New Drug (IND) application to the FDA and begin human clinical trials.

Phase 1 trials involve a small number of healthy people, and are really designed to ensure the safety of the product as a first step. The second phase continues to emphasize safety, with a focus on efficacy as well. These trials typically involve hundreds of people to get preliminary data on whether the product works on their disease.

If the product shows effectiveness, the next step is phase 3 trials, which can include thousands of people and may last several years. Phase 3 studies assess efficacy and safety of a product against a comparator, such as a placebo, in a broad sample of the patient population.

Following these trials, the sponsor submits an application to the FDA to review the data and make a decision as to whether the product is appropriate for use in the marketplace. Because Aduhelm received accelerated approval, Biogen is required to conduct phase 4 – or post approval trials – and provide the FDA with additional data on the product’s efficacy against memory loss and cognitive decline in Alzheimer’s patients.

How did the approval process of the Biogen drug differ from COVID-19 vaccines?

Prichep: The FDA has different pathways to meet public needs. The emergency use authorization (EUA) issued to COVID-19 vaccines enables rapid response to public health crises. EUAs require rigorous criteria to be met but are not approvals. With products like [aducanumab], one may see accelerated approvals and fast-track approvals, which are pathways established to fill critical unmet needs in treating different diseases. So when there's a lack of treatment options or nothing on the market that can help people with a certain condition, these pathways offer a way to get treatment out to patient populations more quickly.

The accelerated approval process allows the FDA to issue its approval based on a proxy, or what’s known as a surrogate endpoint. In this case, instead of basing approval on cognitive benefit, the FDA looked at whether this medication reduces the plaques (when protein pieces clump together) in the brain that are a contributing factor to Alzheimer’s disease. That's what [aducanumab] was approved upon – that the medication has an impact on those plaques. That was shown in trials. Whether or not that will have a meaningful impact on cognitive decline is what we're waiting to see from the marketplace data.

This approval is controversial. The FDA approval comes despite their Advisory Committee’s vote to not approve. So, the scientific community is not 100% on board with this product moving to market at this time. To the FDA’s credit, they've had expedited pathways for decades and aim to be responsive to unmet health needs of the public in a way that's still safe and looking to ensure efficacy.

What will happen next now it’s been approved?

Prichep: Now that aducanumab has accelerated approval from the FDA, the company is able to manufacture and distribute the infusion.

What they’ll be looking to do is educate physicians on the product, ensure that there's coverage from insurance providers, that there's enough supply to go out to people. But what's really important to keep in mind is the product had an accelerated approval, meaning it's conditional.

More data needs to be collected and ultimately provided to the FDA to assess whether this is a product that is truly providing cognitive benefit in patients with Alzheimer's disease. So what really needs to be figured out is how that data is going to be collected and used. What is the data that's needed? And what are the timelines for that?

There’s the go-to market strategy of how does the manufacturer get this product to patients, but there's also that really critical piece of how can the manufacturer collect the data that's needed to validate whether this product should continue to be available to the public based on its efficacy and safety profile.

Will it then also be available in other countries besides the US?

Prichep: Countries have different regulatory processes. Some are more similar than others, but the approving regulatory authorities have different mandates and different requirements that must be met. The EU would look to do their own regulatory review before approval, as you saw with the COVID-19 vaccines.

McCain: I foresee a lot of other countries looking to the US and a system in which they are openly sharing what the data actually is and what the outcomes are. This will help some of the other countries, especially where the burden of Alzheimer’s and dementia is really high, in the low and middle-income countries. A lot is going to be dependent on how the drug performs in the US and hopefully will create a pathway for others to follow.

Are you hopeful the market reaction will encourage investment in research for other treatments?

McCain: The market responded positively to the recent approval, which is a signal that investors may be willing to invest more in science and research – and hopefully will help to reinvigorate investment in the Alzheimer’s and dementia space, and get these portfolios back on track.

Prichep: There’s been a lot of discussion and excitement about whether medications can get to market faster following the EUAs of COVID-19 vaccines. But there's a big difference between the COVID vaccines and products like this. With diseases like Alzheimer’s, there's still so much research that needs to go into understanding what's really causing this disease and how to develop a targeted product that can work on it. There's so much trial and error.

In the Alzheimer's space, we've seen peaks and valleys in investment. Just a few years ago, there were numerous companies running promising trials and then the products failed to provide a benefit. Companies pulled back on investments because they couldn't figure out how to make a product that effectively worked in Alzheimer’s disease. So, with this approval, I am hopeful for more investment and optimistic about progress, but we need to remember that finding treatments for this disease is exceedingly complicated.

What is also interesting, as I think about this approval, is the potential future use of the accelerated approval pathway. As we're starting to understand more about genetic drivers of disease, how might companies who are looking at targeting certain genes or certain markers of a disease use this accelerated approval pathway? What is the comfort level with approving products that have yet to show clinical benefit? As we move ahead in the genetic revolution in medicine, I expect more difficult questions along those lines balanced with new opportunity to meet unmet medical needs and improve lives.