Q&A With Dr. Stephen Salloway: Implications of the FDA Aducanumab Decision

Biogen’s aducanumab — a human antibody-based drug that targets beta-amyloid plaques, which are found in the brains of people with Alzheimer’s — has gone through a path filled with twists and turns. In November 2020, FDA advisers overwhelmingly said the pharmaceutical company failed to prove that the drug is effective in treating Alzheimer’s. But results from the drug’s clinical trials are complex and hotly-debated, and the FDA is expected to determine its fate by June 7.

With less than a month away from the much-anticipated verdict, Being Patient spoke with Dr. Stephen Salloway, a principal investigator of the aducanumab clinical trial and the director of Butler Hospital’s Memory and Aging Program, about the drug’s trial results and how the Alzheimer’s community could meet the challenges of administering it to patients if the FDA gives the nod of approval.

There are many implications to consider, according to Salloway and other experts. For one, if the FDA approves the drug, amyloid tests would most likely be needed for patients. While PET scans measuring amyloid plaques aren’t covered by Medicare, spinal taps (also known as lumbar punctures) would be more accessible options. After all, they are typically covered by Medicare and other providers. Clinicians are hopeful that blood tests would help fill the gap for measuring amyloid and tau, another Alzheimer’s biomarker.

Ultimately, experts say that effectively treating Alzheimer’s will require more than just one “magic bullet” drug — rather, they anticipate that a cocktail of drugs will likely be necessary. Read on for our conversation with Salloway about the implications of the aducanumab outcome.

Being Patient: Can you give us a brief overview of how aducanumab works, and results from clinical trials? 

Dr. Stephen Salloway: It’s interesting how this drug was developed because it’s a little bit different from some of the other antibodies. Right now, you hear on TV a lot of medicines advertised with ‘mab’ at the end. That stands for monoclonal antibodies. What happened with aducanumab is that the company that was developing it before Biogen looked at older people who lived a long life and either didn’t get Alzheimer’s or had a very slow form. The company surveyed these people and looked for antibodies that might be retarding that Alzheimer process in the brain. The lead drug they found was aducanumab. This is actually a human antibody that has now been manufactured and it’s given by infusion.

The drug gets into the brain at very low concentrations and it binds to the amyloid plaques that build up in Alzheimer’s. Then, it stimulates the immune system to help break up the plaques and remove them. It looks like it does this pretty well, that it does lower the plaque build up. It actually got off to a really good start in the early phase trial, which showed that there we were slowing down cognitive decline. 

In the longer Phase 3 program to reproduce that result, Biogen did an interim analysis a year prior to the end of the study when everybody had already been enrolled and half had finished. They found that the drug probably wasn’t going to meet its primary outcome and they decided to terminate the trial early. Then, they looked at all the data after they had it for everybody and they found that at least one of the two trials was working. 

Being Patient: In November, FDA advisors rejected evidence supporting the benefits of the drug. Can you summarize what happened at that meeting? 

Dr. Stephen Salloway: The FDA clinical staff looked at the data very carefully and worked with Biogen. They gave it a positive review. They thought that there was benefit and the drug was certainly worth considering. 

Then, they had a group of outside experts review the data. The data is a little bit complicated. The trial ended early. We increased the dose so not everybody got to the highest dose. There were a number of issues with the data. There are investigators like myself who have had a lot of experience and view this as beneficial to people, the opening of a new era for the treatment of Alzheimer’s. But you can also look the other way and say, ‘Geez, I’m not sure if the data is strong enough. Maybe we should wait and do more research.’

Being Patient: From your experience of studying the drug, what can you tell us about its effects for patients in clinical trials? 

Dr. Stephen Salloway: I’ve had a lot of experience with this drug. I’ve been involved with the development of it right from the beginning in people, and I probably have treated the most people in the world, I might say, on this drug. 

Because the first trial lasted for a year against placebo and then everyone would continue on active medicine, we’ve had many people at our center who’ve been on aducanumab for more than five years and on active treatment. 

Want to learn more about clinical trials
for Alzheimer’s and dementia?
Check out the Lilly Trial Guide.

The good news is that the majority of people that were on it actually stayed pretty stable over a pretty long period of time, which is not typical for Alzheimer’s because Alzheimer’s gets gradually worse. Preserving quality of life in early stages of Alzheimer’s is worth a lot, and families who at least had this stability really appreciate it. 

Being Patient: Would people need to stay on aducanumab for life? 

Dr. Stephen Salloway: We don’t know the answer to that. We know that amyloid lowering does take place after a year and 18 months, and it continues up to a certain point. But we don’t know how long someone really needs to get those monthly infusions. If they get to a point where they’re considered amyloid negative, or they don’t look like they have Alzheimer’s on the PET scan, is that a good time to stop? 

Lilly has been testing a similar drug called donanemab. They had good results from a recent trial that showed lowering of amyloid and also a slowing down of memory loss. They stopped the medicine once someone got to a normal range of amyloid. 

Being Patient: What are the side effects of aducanumab? 

Dr. Stephen Salloway: The main one is what’s referred to as amyloid-related imaging abnormalities (ARIAs). We found that when you remove the amyloid from the brain you also remove amyloid from blood vessels as well, especially in ApoE4 carriers, and that can cause a little bit of leakiness in the blood vessels, especially early in treatment, usually in the first six months. 70 percent of the time there are no symptoms, but there can be some mild symptoms. We monitor for that. It shows up on an MRI scan.

We’ll see what the FDA says, but at least during the first year, I think people should have safety MRI scans every three months to monitor for that, and then sometimes we have to adjust the medicine. It almost always goes away on its own if we wait for it to clear. 

Being Patient: If the FDA approves aducanumab, how could we tackle the challenge of monitoring the levels of amyloid plaques when PET scans are largely inaccessible? 

Dr. Stephen Salloway: I don’t know what the FDA is going to say, but I strongly suspect that there will need to be an amyloid test. In many cases, the spinal fluid test is covered by Medicare and some other providers. Maybe we start out looking at spinal fluid because of the coverage, and the cost is lower for the spinal fluid test than the brain scan. 

Most people in the U.S. prefer the brain scan because they’re a little frightened of spinal taps. I’ve done thousands of spinal taps. It’s not a big procedure, but a lot of people are nervous about it.  

There’s a lot of discussions underway with Medicare right now to cover the amyloid PET scans as well. We’re really going to need that. If it’s not immediately after the approval of aducanumab, hopefully soon after there will be a parallel approval for the PET scan [as of October 2023, amyloid PET scans are covered by Medicare] . 

The solution here is a blood test. It’s going to be way cheaper and much more widely available. Any doctor is going to be able to order it and so forth. I’m really excited about it. We’re right on the verge. We’re using it now for research to screen for trials and I think we got to get them into the clinic as quickly as we can validate them. My message to the powers that be, and I want to be part of that solution, is let’s get those blood tests ready for clinical use. 

Being Patient: How do we address the shortage of memory specialists if the drug is approved? 

Dr. Stephen Salloway: This is critical to this particular treatment but also future treatments for Alzheimer’s once we have blood tests and everything else. There aren’t enough memory specialists to take care of the millions of people in the United States. More people are going to have to get involved. 

This is going to require a real community response if this drug is approved. Because it’s given by infusion, we’re going to need infusion centers for aducanumab. Millions of people will be eligible for the treatment so we have to figure out how to give the medicine, how to monitor for its safety. Radiologists have to learn how to recognize ARIA that shows up on MRI. 

We need to bring more providers into the mix to make this happen. I look forward to it. It’s going to be a big challenge, but an important one. I call Alzheimer’s the epidemic within the pandemic. Underneath COVID, Alzheimer’s is brewing.

The interview has been edited for length and clarity.

Contact Nicholas Chan at nicholas@beingpatient.com