Harry Johns is ready to stop talking about whether or not the Food and Drug Administration should have approved Aduhelm, the divisive new Alzheimer’s treatment that got the green light last week.
“Dwelling on the approval at this point is not productive for those who can benefit from the treatment,” said Johns, the CEO of the Alzheimer’s Association. The “negative voices” focused on criticizing the decision, he said, are “not pro-patient.”
Instead, Johns said, it is time to think about “how we can get an approved treatment to the people who would most likely benefit, with it covered, with a price that would make it accessible to all communities, so it does not drive inequity, but it in fact drives access for everyone.”
It is a blunt perspective that offers a rebuke to the experts who have questioned the clinical trial data and regulatory process associated with the drug’s approval. But Johns hit Aduhelm’s maker Biogen as well for setting what the association called a “simply unacceptable” price of $56,000 for the therapy.
Johns also pushed Biogen to move fast with the confirmatory trial required by the FDA under the approval, though he declined to say just how quickly the trial could be done.
“Nine years is a long time, I’ll say,” Johns said, referencing what Biogen executives have said their timeline could be for reporting the results of the trial.
By and large, though, Johns is, like Biogen, jubilant about the new option for patients. He, like the company’s executives, said that Aduhelm should be prescribed for patients like those who were in the trials: people in the early stages of the disease with amyloid protein plaques. It’s expected that payers will likely set policies to limit coverage to those people as well. (Biogen contributes to the association, though the group has noted drug company donations are a tiny fraction of their overall budget and said that the funding doesn’t influence its decisions.)
STAT spoke with Johns this week over Zoom. Excerpts from the conversation are below, lightly edited for clarity.
When we spoke in your office in December 2019, I asked if the FDA should approve what was then called aducanumab and you took a neutral position. But the association wound up advocating for its approval. How and why did you decide to endorse the therapy?
We came to the conclusion that the science was sound for what is a very large population of people who have not had treatment. Now, clearly, this is not a cure, and it is a marginal difference for people, but a marginal difference can make a real difference for people who have only the devastation of Alzheimer’s to look to. So looking at all the science, looking at all the impact, we chose to strongly endorse approval.
If it’s not a cure, how should patients and families view Aduhelm? In talking with neurologists, they say one of their first jobs is setting expectations.
I think that’s right. We want people to understand that it can make a difference for them, but we don’t want them to think it is going to absolutely change their course. But it is the first treatment that targets the underlying disease, rather than just symptoms. So we’ll be working with people to have them understand that. The patient community — persons with dementia and their caregivers — are excited to have something that can make a difference in their lives.
I’m going to push on that because both what you’re saying now, and in the statement you put out last week when the approval was announced, you and the association have said things like Aduhelm “delays decline” or “slows progression.” But even the FDA said in its statements about the approval that the clinical benefit wasn’t clear. So how can you say that?
The successful trial — and there was a successful trial — showed 22% improvement in what is effectively the cognitive functional side of people’s lives. FDA ultimately approved on what is the amyloid clearance, but the trial showed that for people with mild cognitive impairment due to Alzheimer’s disease or first-stage Alzheimer’s dementia, that it can make a difference. And that difference for people who otherwise are going to decline is real.
What about the other trial that found no benefit? Do you discount it?
Most of the trials, if not all of the trials, with amyloid-clearing drugs are dose escalated. So if you look at the timeline at what occurred, the dose was escalated not all that long before they pulled the futility data [at a prearranged time]. Then it took time for them to do the analysis. So in that time that they did the analysis, people had dose escalation for a longer period. Those are the people who appear to have benefited. This is all consistent with years of accumulated science on Alzheimer’s, and particularly on amyloid as an approach. On this kind of a treatment, that dose escalation was important. So with this trial it would be reasonable to assume that it would actually be beneficial if it went longer.
So your question was specifically about the other trial, you said “discount it.” We believe the FDA did the right thing, which is [approve Aduhelm based on] one positive trial and other science evidence. That’s how they got to their decision, and we believe that is correct.
The FDA approved Aduhelm on a so-called surrogate endpoint, looking at how the drug cleared amyloid plaques, rather than on clear clinical evidence. Should other therapies that have shown a reduction in amyloid be approved then even if they haven’t demonstrated a clinical benefit?
Well, we believe this treatment has demonstrated benefit. And you will recall, too, we called for approval, but approval with a confirmatory trial.
So if Aduhelm fails its confirmatory trial, should it be taken off the market?
If the drug does not demonstrate effectiveness, then we certainly don’t want our constituency to be trying to pursue treatment that isn’t successful.
Some of the people who are pushing back on the way the FDA did this, they don’t seem to understand that these kinds of approaches are taken in other disease categories. This is not new conceptually overall. It is new to Alzheimer’s because we haven’t had a drug in 18 years and certainly we’ve never had one that improves the potential path of the underlying disease. There seems to be a lack of understanding of what’s occurred in other diseases that’s consistent with what the FDA’s done now in Alzheimer’s.
The association over the weekend called Biogen’s list price of $56,000 “simply unacceptable.” What would a fair price be?
We don’t see ourselves as experts in price setting, but that price seems pretty clear on its face to be simply unacceptable. We are here to drive science and set what is the path to facilitating approval, not just for this treatment — this is not our treatment, we have no specific interest in this company or treatment — but we have an interest in getting treatments overall to the constituency. But we don’t believe we’re the pricing experts.
But if you see a price and see it as unacceptable, surely there’s a price out there that you would see as acceptable.
That’s not necessarily true. We believe it’s up to the company and payers. But we believe that the price is unacceptable because we are so concerned that No. 1, it would cause out-of-pocket costs for so many people that would be so high that it would not reach the number of people it otherwise could. And with a price so high, we’re even more concerned that it would drive more inequity in terms of distribution of a treatment we believe will make a difference for people. We want all communities to have access.
Have you spoken with Biogen about the price?
What have your conversations been like with the company both in the months leading up to the decision and in the last week?
I can tell you flatly, no senior member of our team — myself, anyone else — had talked to Biogen at all until after we were pursuing our interest in approval by the FDA. Now after those campaigns, we opened a channel for discussion, but really then primarily for what can be done for the patient community, what can be done for those who can benefit. No conversation, none, zero about pricing.
But surely they would take your call about your concerns about pricing? I guess the question is, what are you going to do beyond putting out that statement?
We are going to work with payers, who are the ones who will ultimately establish what can reasonably be paid. We will continue to make it clear to everyone what needs to be done, which is Biogen reducing the price to a level such that out-of-pocket expenses can be borne by people with really all communities having access.
Two months or so after the advisory committee hearing, the association organized a virtual meeting between patients and caregivers and FDA officials because you felt their voices weren’t adequately heard during the hearing. What happened there? Do you think the broader patient and association advocacy had some influence here?
I’d certainly like to think that our advocacy had some influence. In fairness, I think the FDA believes in supporting patients. And I think they’ve demonstrated that with their approval with a confirmatory trial rather than waiting for years to get to an approval. So at the listening session that the FDA was willing to hold with our constituents — these were people, most of whom have a diagnosis today of Alzheimer’s, there were some caregivers there too — you cannot be unmoved by hearing the stories of people who face this disease, the crushing realities of it every day. And that’s been the response to the approval too. They’re happy to have some possibility, and that’s the way they described it to the FDA.