Jeff Borghoff knew something was wrong after his face went into a twitch and then a sadness. When he was diagnosed with early Alzheimer’s disease at age 51, his greatest fear was a rapid decline in his mental abilities.
Desperate to keep the condition at bay, the former IT executive signed up for the clinical trial of Biogen’s experimental Alzheimer’s drug, aducanumab. Six years later, Borghoff attributes the controversial treatment to valuable extra time with his wife and three children.
“Our fear was always that there would be a strong decline in all my mental abilities, but until now that hasn’t been the case,” he says. “I’ve had some symptomatic issues… but the medication is really about more time, more time with my loved ones, those are crucial things.”
Now, following the drug’s approval this week by the US drug regulatory agency, many of the estimated 35 million people with Alzheimer’s around the world will be waiting in line for their own infusion of hope.
Yet there is a sting in the tail of what seems unequivocally good news for patients. A range of issues, ranging from the cost of the drug to questions about the evidence of its efficacy, will put pressure on health systems already battered by the pandemic, which may be ill-equipped to meet the expectations that have been raised.
The drug’s approval threatens to open a political and business divide between the US — where a price tag of $56,000 a year has been set — and Europe, where many governments may be far more skeptical about its value.
Complicating the debate is a growing chorus of anger over the FDA’s decision to green-light the drug in the first place, given the scant evidence of its efficacy. Three leading scientists resigned from their advisory boards this week, in an outrageous rejection of a supposedly objective and data-driven approval process.
Biogen originally abandoned the drug after a futility analysis suggested it was ineffective. But when it examined a larger data set, it found that patients who took a higher dose “experienced significant benefits on measures of cognition and function such as memory, orientation and language.”
Craig Garthwaite, a professor of hospital and health services at Northwestern University, says it is “terrible” that the FDA has given in to patient groups and not listened to its scientific advisors. He says he is “stunned” by “this idea that even if we don’t know or even if it doesn’t work, we should try to give people hope.”
Still, experts believe health insurers will likely feel obligated to cover the drug now that it’s FDA-approved. In an unexpected twist, the regulator approved it for all patients with the condition — rather than just those with the early-stage disease, who were studied in the clinical trial.
Most U.S. patients will use Medicare, the public health insurance provider for the over-65s, which Biogen told investors it expects to cover the “vast majority” of patients. Some experts predict that this will soon become Medicare’s largest expense for physician-administered drugs.
The potential costs go far beyond just the drug. The need to administer it seems to challenge established patterns of care for people with dementia, creating a need for different types of staff and expensive equipment not typically associated with treating the disease.
Estimates from Premier, a group that represents more than 4,000 U.S. hospitals, the cost of the drug’s intravenous infusion, radiology and imaging could add between $2,000 and $15,000 or even more to the drug’s price tag.
David Thomas, head of policy for Alzheimer’s Research UK, says “great concern for people with dementia” [in the UK] is done from memory clinics, which are largely staffed by old age psychiatrists”. Unlike a neurologist, these doctors “often lack experience in the diagnostics and monitoring needed to administer disease-modifying treatments.”
The other big challenge, he emphasizes, is securing the necessary equipment. Diagnoses for those suspected of having the disease usually involve low-key cognitive tests, which don’t require special hardware.
To be eligible for aducanumab, a patient must have a certain level in their brain of amyloids, proteins that can accumulate in tissues or organs, which is determined by a positron emission tomography (PET) scan or the more invasive, but usually less expensive , lumbar tap, which removes fluid from the spine.
Eligible patients must then undergo an intravenous infusion of aducanumab once every four weeks and undergo regular MRI scans that can detect dangerous side effects such as brain swelling and bleeding.
When Alzheimer’s Research UK recently surveyed psychiatrists in the country, “the majority said it would take up to five years to be ready to administer treatment – only a third thought they could do it in a year”. says Thomas.
Sanjiv Sharma, Borghoff’s physician and founder of the Advanced Memory Institute of New Jersey, recognizes the obstacles ahead if it is to reach all those who could potentially benefit. But he has no doubt that the US must lead the way. “If we can’t do it [here], as the most developed country in the world, where can we do that?” he says.
‘A financial incentive to use the drug’
Soeren Mattke, director of the Center for Improving Chronic Illness Care at the University of Southern California, states that underdeveloped countries are currently well prepared to administer the drug, let alone middle-income countries and emerging countries such as China and Brazil with much less. advanced health infrastructure.
However, in the US, prepared funding for the treatment will spawn its own business models, he suggests. Medicare pays doctors a fee of 6 percent of the drug’s price, plus infusion and visitation costs.
“The US is very enterprising for once . . . the neurologists or psychiatrists or geriatricians realize, ‘Well, I can really live off this by distributing the drug through my practice,’ that’s a very powerful pull to set up the diagnostic facilities to find the patients,” he says .
This could pose its own conflicts of interest, Northwestern’s Garthwaite suggests. “There is an actual financial incentive to take the drug, even if you don’t think it’s going to work.”
Mattke also acknowledges that the same incentives do not exist in more regulated, government-funded health systems like Canada and the UK, where lengthy approvals and limited budgets can limit equipment purchases or the ability to hire new staff.
“I’m a little nervous about government-imposed changes because we all know that governments don’t act very quickly,” he adds.
In the US, Biogen has helped prepare more than 900 infusion sites in the US to administer the drug. It expects “modest” revenue in 2021, but a multi-billion dollar opportunity in the coming years, as it could be given to between 1 and 2 million patients in the US alone.
Roni Christopher, vice president of design and intervention in the analysis group at Premier, has spent the past year exploring everything from developing standard assessments of a patient’s cognitive status to training radiologists to recognize side effects and even assess whether infusion sites have adequate seating.
Even with these logistical insights, the most experienced health systems may not be ready to treat patients until the fall. The FDA’s decision to open the drug to all Alzheimer’s patients will spark a “bigger tidal wave” of interest, Christopher says.
“The pressure from consumers or patients will dictate a lot here because it is such a devastating disease,” she adds.
Value for your money?
Even bigger than the question of how the drug should be delivered is how much health systems — and the taxpayers who fund them — will be willing to pay for a drug with so little proven impact.
In parts of Europe, where so-called “health technology assessments” are used to assess the value for money of a new drug, the battle has yet to be seriously fought over whether the drug should be offered to patients. In the UK, where the National Institute for Health and Care Excellence has considerable international influence, officials are personally concerned that expectations are being raised that will not be easily met.
Umer Raffat, an analyst at Evercore ISI, expects that even if aducanumab gets the green light from European authorities, they will allow “no price above $10,000” per year, which will put Biogen in a difficult position to decide whether to the US sells at five times the European price.
This difference in approach seems to wake up Republican politicians who believe that other countries negotiating cheaper drug prices are in fact decoupling US innovation.
On the other side of the political aisle, some Democrats are using the price set by Biogen as evidence that Medicare should be allowed to negotiate prices — a potential bargaining power with the drug industry that the government doesn’t over-exert.
Murray Aitken, executive director of the IQVIA Institute for Human Data Science in New Jersey, believes the question of how much health systems should pay for a drug that, however flawed, offers a rare hope of hope could lead to a much-anticipated public reckoning on whether European governments should spend a larger share of gross domestic product on health.
He adds: “It could spark a bigger conversation for us as a civil society, in terms of how we distribute our wealth . . . It could spark that wider civic debate and discussion, which I would say is probably too late.” is.”
Back home in New Jersey, Jeff Borghoff has no doubts about the value of the drug he believes has prolonged his life. “I know it’s not a cure and probably won’t fix everything damaged in my brain from Alzheimer’s disease,” Borghoff says. He adds, “I’m 57. I’ll be fine if I live in my 70s, that will be a good run and I hope the medication will help me with that.”