John Dwyer, GAP President, spoke about the impact Abucanumab will have on Alzheimer’s research and clinical trials going forward.
The arrival of the first new Alzheimer’s drug in two decades should have been a moment of celebration. But so far, the healthcare industry is feeling concerned.
The US Food and Drug Administration approved the new medication, called Aduhelm, on June 7. The drug, made by the biotech company Biogen, is designed to remove a sticky plaque that builds up in the brains of some people with Alzheimer’s, which it did in clinical trials. But it isn’t clear that using the drug to clear this plaque leads to an improvement in memory and cognition.
“I don’t believe that the drug provides benefits,” Dr. David Knopman, a neurologist at the Mayo Clinic, told Insider. Knopman worked with Biogen on trials of the drug but was so opposed to its approval that he resigned as an FDA advisor this week. Two other FDA advisors have also stepped down.
Aduhelm, developed under the generic name aducanumab, actually failed in one late-stage clinical trial and was shelved in March 2019. It was revived later that year when an analysis found that a group of participants in a second trial had benefited from the drug.
Aduhelm will cost $56,000 a year
More than 6 million Americans have Alzheimer’s, according to the Alzheimer’s Association. Caring for them will cost $355 billion this year, including $239 billion in Medicare and Medicaid payments, the association found. A successful treatment would be a huge advancement for people with Alzheimer’s, but Knopman says Aduhelm falls short.
“The unmet need of the people with the disease is as great today as it was on Monday morning before the announcement,” Knopman said. “Aducanumab set a very low bar to exceed.”
The FDA said it approved Aduhelm because the potential benefits outweighed the drug’s risks. It’s requiring Biogen to run more trials to prove that the drug works. In a statement, Biogen said that a reduction in amyloid plaques was “reasonably likely” to predict benefits for patients. CEO Michel Vounatsos added that Aduhelm’s approval would spark innovation for years to come.
Despite its uncertain benefits, Aduhelm, given as an IV infusion once a month, will come with a hefty price tag: about $56,000 a year, on average. The drug-pricing watchdog group Institute for Clinical and Economic Review has said the drug should cost $8,300 or less annually.
The US government would cover much of the bill for Aduhelm
Medicare would end up shouldering much of the cost, because most people with Alzheimer’s are over 65 and eligible for the government insurance plan. The federal government could end up spending more than $14 billion on it, the Bernstein analyst Ronny Gal said.
That’s a significant expense. The drug is likely to be paid for by Medicare’s Part B program, which spent a total of $37 billion on drugs in 2019.
Medical practitioners are already anticipating patients filling their offices to request the drug. Aduhelm’s label gives physicians broad leeway in prescribing it, which could lead to it flooding the Alzheimer’s market.
Some doctors told Insider that prescribers would most likely limit the use of the drug to people in earlier stages of the disease. It’s unclear how that would play out and how insurers would cover the drug.
Experts fear that it could cannibalize the already low number of people with Alzheimer’s who are available and willing to participate in trials of new treatments, making it harder to develop better treatments.
“How you’re going to get subjects to enroll and how you’re going to measure the effects of your new drug is what we in the academic setting are worried about,” said James Brewer, a neurologist and professor at the University of California San Diego.
Aduhelm’s approval is expected to boost investment dollars, but not investment in better treatment strategies
One upside of Aduhelm’s approval is that it’s likely to lead to an influx of investment in companies working on Alzheimer’s treatments, analysts such as Jefferies’ Andrew Tsai have said.
Several companies developing these treatments or diagnostic tools experienced a stock-price bump this week.
But some medical experts fear that Aduhelm’s approval will ultimately plow even more money into drugs that work in a similar way — by targeting amyloid plaques in the brain — rather than aid the search for new ideas.
“One possibility is it stimulates more money in general — that would be great. But I think it’s more likely to promote the status quo,” said George Perry, a neurobiologist at the University of Texas at San Antonio. “There might be more money in total, but the big money will continue in amyloid.”
The so-called amyloid theory of treating Alzheimer’s continues to be controversial. Amyloid is one of the few firm characteristics of the disease that scientists have been able to grab on to — but time and time again, clearing the plaque hasn’t definitively stopped memory and cognition deterioration.
Perry, a longtime skeptic of the amyloid theory, predicted that Aduhelm’s approval would keep “putting good money in a bad place.”
“The amyloid approach has paralyzed the field for 30 years, and people will keep betting on putting more money where it hasn’t gone anywhere,” he said.
Still, many drug companies are seeking new avenues for addressing Alzheimer’s.
Some are focusing on another protein found in patients’ brains called tau. Others are targeting immune cells in the brain that are thought to be doing a poor job of clearing out amyloid and tau proteins or becoming overactive and damaging nervous-system cells.
Very few eligible people enroll in trials of Alzheimer’s drugs, leading to delays
Whether they were in favor of or opposed to Aduhelm’s approval, experts told Insider that more treatment options are needed.
To develop those treatments, we’ll need more clinical trials of Alzheimer’s drugs. But getting those trials up and running isn’t easy.
Just 1% of eligible patients are referred to or consider participating in a clinical trial, a paper from the University of Southern California found. That’s because we don’t have very good ways of diagnosing the disease, and diagnosing it can take a long time.
About 90% of clinical trials of Alzheimer’s treatments are delayed because of slow enrollment, research suggests.
Some people with Alzheimer’s and their caregivers will want to take their chances with an FDA-approved drug like Aduhelm rather than an experimental drug in a trial, Michael Greicius, a neurologist, and G. Caleb Alexander, an FDA advisor, wrote last month in a New York Times opinion article. Taking Aduhelm could also make patients ineligible for clinical trials, because the drug carries a risk of brain swelling.
John Dwyer, the president of the clinical-testing organization Global Alzheimer’s Platform Foundation, thinks one silver lining is that the high cost of Aduhelm may push people into drug trials.
“There are going to be plenty of people eager to get on drug therapy. Now they’re going to believe that there is new science that can work wonders,” he said. “They’re going to want to get it, but they can’t afford aducanumab, so they’ll look for trials.”
Drugmakers will need to change the way they run trials of Alzheimer’s drugs, experts say
Regardless of how many people end up taking Aduhelm, drugmakers will most likely need to adapt.
Though Knopman was against Aduhelm’s approval, he’s come around to the idea that it might not spell disaster for other drug trials.
He pointed to another neurological disorder, multiple sclerosis, which causes the immune system to attack and damage nerves. Since the treatment interferon beta was approved in the 1990s and set a new standard of care, several new therapies have managed to make it through testing and to the market. But drugmakers had to change their approach, focusing on smaller groups of patients with unique disease characteristics.
Alzheimer’s-drug makers could also take a page from cancer-drug developers who’ve embraced the paradigm-shifting therapies that have hit the market in the past decade by running trials that compare treatments or that test several at once to see if they work better together.
Athira Pharma, a small drugmaker in the Seattle area, is one of the companies that’s gotten a stock boost from Aduhelm’s approval. Chief Medical Officer Hans Moebius led the research team that developed the last major Alzheimer’s drug, Namenda, which was approved in 2003.
Moebius isn’t convinced that Aduhelm works all that well. But he said its approval confirmed Athira’s drug-development strategy. Athira’s drug doesn’t target amyloid but other elements of the nervous system. So while the company is testing it as a solo treatment, it could be combined with other medications like Aduhelm.
Plus, Athira’s clinical trials are open to people who’ve been on other Alzheimer’s drugs, making it easier for the company to continue recruiting patients for its two mid-to-late-stage clinical trials.
“Will it be more difficult for a non-Aduhelm drug to recruit for its trial? The answer is absolutely yes,” Dwyer said. “We all have to put on our clinical-trial big boy and girl pants and get this solved.”
Originally posted by Business Insider on June 14, 2021.