Mark Goldstein, MD, CPI, President and Principal Investigator, JEM Research Institute, talks about a drug that may be bringing positive results for Alzheimer’s patients.
What were you looking for in the trial you conducted on the Alzheimer’s drug?
GOLDSTEIN: The original trial, which I believe started around 2016, used Aducanumab as a monoclonal antibody to attach to amyloid protein in the brain and remove it. The study was ultimately stopped in the first quarter of 2019 because there were some concerns about how well it was working. Eventually, we looked at the data and saw a very positive signal for how the drug may have been helping people. So, Biogen reinitiated a trial using the same drug in which everybody then got the drug, and no one got placebo. That trial is currently ongoing while the FDA is reviewing the results of the previous trial to see whether the drug will be approved for use in the general population of people with Alzheimer’s disease.
What is the purpose of the second trial?
GOLDSTEIN: The second trial is for efficacy, or how well it’s working. But, because many things had gone on for those subjects in the time between the start of the new trial and the ending of the old trial, I think safety is certainly one of the aspects of the new trial that they’re looking at carefully.
Can you explain the science of how exactly this drug, Aducanumab, works with the amyloid in the brain?
GOLDSTEIN: The accumulation of amyloid in the brain is certainly part of the puzzle that leads to the clinical recognition of the condition that we call Alzheimer’s disease. It’s not the entire answer, but it’s part of it. This drug is designed to help prevent the further deposition of amyloid in the brain and perhaps as well to remove existing amyloid in the hope that in so doing, it will at least slow down worsening, if not stabilize the patient’s condition.
Walk us through what the patients had to do when they were given this drug during the trial?
GOLDSTEIN: Patients would come once a month for an intravenous infusion of the medication. The infusion would take an hour, maybe two hours. Patients tolerated it very well and would then remain at the site for a period of time for observation. Periodically, there were safety labs that were done and safety MRI scans to make sure there were no potential side effects from the administration of the medication.
Were they given this once a month for the entire trial?
GOLDSTEIN: The trial length has varied, but typically a year and a half to two years or so.
For this ongoing trial, is it the same procedure, same method?
GOLDSTEIN: Yes. This trial is a little bit different in that there’s no placebo arm. So, everybody will get the drug. And in addition, everybody’s going to get the high dose of the drug. The original trial allowed patients to get different dose levels depending on how they randomized. In the current trial, patients will be start out with an escalating dose until they get to the high dose of the drug, and then everybody will get the high dose. The reason is because when the data from the original trials was looked at, it was felt that the results favored those patients that got the highest dose for the longest period of time.
What implications do you think this drug will have for the medical world and to Alzheimer’s?
GOLDSTEIN: I would say we hope this is a stepping-stone to what will eventually prove to be part of an effective treatment of this horrible disease. My understanding is that the FDA is going to begin looking at this drug over the next few months. And based on press releases I’ve read, a ruling on it is expected sometime late in the first quarter of 2021.
Who would benefit the most from this?
GOLDSTEIN: The FDA, in conjunction with Biogen and others, will have to decide what the indications are for who should receive this drug. My guess is it will be available for people with the very earliest signs of a cognitive issue that we believe to be due to Alzheimer’s disease. It doesn’t have to be full-blown dementia, but we do believe it should and probably will be available for people that have memory impairment that is on the spectrum to what will eventually become what we consider to be full-blown Alzheimer’s disease, dementia.
Would this drug only be offered to the people in the early stages or are there benefits in late stages?
GOLDSTEIN: The ruling and applicability of this drug is speculation, and I can’t really speak to that. My own feeling is that the people who are most likely to benefit from it will be those that are treated sooner in their course than later.
In regards to the original study, are there any numbers to how effective the drug was?
GOLDSTEIN: That data has been reviewed. I don’t carry those numbers around in my head, but there was benefit from patients who got the drug at the higher dose for the longer period of time, not only in removal of amyloid from the brain, but in the ability to demonstrate better function as well. This is critical because just removing the amyloid from the brain without improvement in function would not be worth the time and effort.
Is the reason it’s once per month because that’s how long it’s effective?
GOLDSTEIN: The once-a-month is based on Biogen’s feeling as to how their drug worked, data that they used from earlier trials to generate the protocol, and basically how they saw the science of their particular drug. Not all drugs of this type are given just once a month, but Biogen obviously felt that was the right way to administer this medication.
The eligibility criteria was early-stage disease for patients on the original trial. Are there any other criteria besides that in the current trial?
GOLDSTEIN: Yes, there are a whole slew of inclusion and exclusion criteria. Inclusion would be things that the patient had to have, and exclusion would be things that would prevent them from being in the trial. Typically, we were looking for people who were early in the spectrum, generally healthy, or if they had medical problems, they were under good control. For example, they weren’t being treated for active cancer or had uncontrollable heart disease or diabetes that was out of control. And they had to have a clear and incontrovertible diagnosis of Alzheimer’s disease or a condition that would lead to Alzheimer’s disease.
What do you believe this drug would mean for somebody’s quality of life, if they’re diagnosed early on, and they’re in the progression of the disease?
GOLDSTEIN: Well, if and hopefully the FDA agrees with the way Biogen sees this medication, it will slow down worsening in people that are properly chosen as being at risk to continue. If it flattens the curve of the development ultimately over time from first diagnosis, perhaps, to requiring a nursing home or around-the-clock care, it would be a great boon to anybody with the properly diagnosed condition.
How could that affect their lifestyles?
GOLDSTEIN: It would hopefully provide more independence for a longer period of time, less stress on the family and other caregivers, reduced medical costs and reduced costs of ultimate placement as in nursing homes or requiring at-home care. The effects could be astronomical and, frankly, stupendous.
How does this compare to other trials for Alzheimer’s?
GOLDSTEIN: At JEM Research, we’re doing many trials on many different drugs because nobody has quite discovered the special sauce at this moment. But I think this drug, again, if the FDA agrees, would be an important first step in what we call a disease-modifying medication, or a drug that can slow down progression of this condition.
Is there something anecdotal you noticed in your patients that you can tell us about?
GOLDSTEIN: That’s a great question. Let me preface my answer by saying in clinical research, we hate anecdotes. The reason being, and I’m not belittling your question, is because we don’t know who’s getting the drug at the time they’re in the trial. Secondly, we don’t know what they would look like if they weren’t getting the drug. And, we don’t know if the drug works or not. So, for all those reasons, anecdotes don’t really carry a lot of weight, which is why we do double-blind, or randomized, clinical trials. But that said, we definitely had patients who were in the trial that when it stopped felt clearly they were not doing as well as when they were in the trial.
Judy took part in the original trial, and she’s doing this new trial now. Did you notice the difference when she wasn’t taking the drug?
GOLDSTEIN: I don’t remember her specific story, but I do know that there were more than a few people who felt the deterioration after the original trial stopped. Now, again, we can’t draw conclusions from that for the reasons I stated, but we had several people who felt that way.
Is there any number, like you’re doing scans, or you’re looking at numbers, after they deteriorated?
GOLDSTEIN: Well, when Biogen re-looked at their data, they concluded that not only did brain amyloid get reduced by whatever measures they used, but that there was definite evidence of less deterioration in people on the higher dose of the drug for a longer period of time. What numbers that correlates to wouldn’t really be meaningful. But in aggregate, they felt very clearly they saw those metrics in a clear fashion, which is why they are taking their medication, Aducanumab, before the FDA in just a week or so.
Is there anything else you feel people should know?
GOLDSTEIN: I always like to talk about the importance of clinical trials and participating in them, because without people who’ve participated in clinical trials, there would be no advancing science. There would be no new drugs. There would be no anything new to treat conditions like Alzheimer’s. So, I fully encourage anybody out there to think about participating in a clinical trial, whether for Alzheimer’s disease or some other condition.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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