Pharmaceuticals

Why We May Never Know Whether the $56,000-a-Year Alzheimer’s Drug Actually Works

The Food and Drug Administration’s approval in June of a drug purporting to slow the progression of Alzheimer’s disease was widely celebrated, but it also touched off alarms. There were worries in the scientific community about the drug’s mixed results in studies — the FDA’s own expert advisory panel was nearly unanimous in opposing its approval. And the annual $56,000 price tag of the infusion drug, Aduhelm, was decried for potentially adding costs in the tens of billions of dollars to Medicare and Medicaid.

But lost in this discussion is the underlying problem with using the FDA’s “accelerated” pathway to approve drugs for conditions such as Alzheimer’s, a slow, degenerative disease. Though patients will start taking it, if the past is any guide, the world may have to wait many years to find out whether Aduhelm is actually effective — and may never know for sure.

The accelerated approval process, begun in 1992, is an outgrowth of the HIV/AIDS crisis. The process was designed to approve for sale — temporarily — drugs that studies had shown might be promising but that had not yet met the agency’s gold standard of “safe and effective,” in situations where the drug offered potential benefit and where there was no other option.

Unfortunately, the process has too often amounted to a commercial end run around the agency.

The FDA explained its controversial decision to greenlight the Biogen pharmaceutical company’s latest product: Families are desperate, and there is no other Alzheimer’s treatment. Also, importantly, when drugs receive this type of fast-track approval, manufacturers are required to do further controlled studies “to verify the drug’s clinical benefit.” If those studies fail “to verify clinical benefit, the FDA may” — may — withdraw them.

But those subsequent studies have often taken years to complete, if they are finished at all. That’s in part because of the FDA’s notoriously lax follow-up and in part because drugmakers tend to drag their feet. When the drug is in use and profits are good, why would a manufacturer want to find out that a lucrative blockbuster is a failure?

Historically, so far, most of the new drugs that have received accelerated approval treat serious malignancies.

And follow-up studies are far easier to complete when the disease is cancer, not a neurodegenerative disease such as Alzheimer’s. In cancer, “no benefit” means tumor progression and death. The mental decline of Alzheimer’s often takes years and is much harder to measure. So years, possibly decades, later, Aduhelm studies might not yield a clear answer, even if Biogen manages to enroll a significant number of patients in follow-up trials.

Now that Aduhelm is shipping into the marketplace, enrollment in the required follow-up trials is likely to be difficult, if not impossible. If your loved one has Alzheimer’s, with its relentless diminution of mental function, you would want the drug treatment to start right now. How likely would you be to enroll and risk placement in a placebo group?

The FDA gave Biogen nine years for follow-up studies but acknowledged that the timeline was “conservative.”

Even when the required additional studies are performed, the FDA historically has been slow to respond to disappointing results.

In a 2015 study of 36 cancer drugs approved by the FDA, only five ultimately showed evidence of extending life. But making that determination took more than four years, and over that time the drugs had been sold, at a handsome profit, to treat countless patients. Few drugs are removed.

It took 17 years after initial approval via the accelerated process for Mylotarg, a drug to treat a form of leukemia, to be removed from the market after subsequent trials failed to show clinical benefit and suggested possible harm. (The FDA permitted the drug to be sold at a lower dose, with less toxicity.)

Avastin received fast-track approval as a breast cancer treatment in 2008, but three years later the FDA revoked the approval after studies showed the drug did more harm than good in that use. (It is still approved for other, generally less common cancers.)

In April, the FDA said it would be a better policeman of cancer drugs that had come to markets via accelerated approval. But time — as in delays — means money to drug manufacturers.

A few years ago, when I was writing a book about the business of U.S. medicine, a consultant who had worked with pharmaceutical companies on marketing drug treatments for hemophilia told me the industry referred to that serious bleeding disorder as a “high-value disease state,” since the medicines to treat it can top $1 million a year for a single patient.

Aduhelm, at $56,000 a year, is a relative bargain — but hemophilia is a rare disease, and Alzheimer’s is terrifyingly common. Drugs to combat it will be sold and taken. The crucial studies that will define their true benefit will take many years or may never be successfully completed. And from a business perspective, that doesn’t really matter.

Source

Seniors Face Crushing Drug Costs as Congress Stalls on Capping Medicare Out-Of-Pockets

Sharon Clark is able to get her life-sustaining cancer drug, Pomalyst — priced at more than $18,000 for a 28-day supply — only because of the generosity of patient assistance foundations.

Clark, 57, a former insurance agent who lives in Bixby, Oklahoma, had to stop working in 2015 and go on Social Security disability and Medicare after being diagnosed with multiple myeloma, a blood cancer. Without the foundation grants, mostly financed by the drugmakers, she couldn’t afford the nearly $1,000 a month it would cost her for the drug, since her Medicare Part D drug plan requires her to pay 5% of the list price.

Every year, however, Clark has to find new grants to cover her expensive cancer drug.

“It’s shameful that people should have to scramble to find funding for medical care,” she said. “I count my blessings, because other patients have stories that are a lot worse than mine.”

Many Americans with cancer or other serious medical conditions face similar prescription drug ordeals. It’s often worse, however, for Medicare patients. Unlike private health insurance, Part D drug plans have no cap on patients’ 5% coinsurance costs once they hit $6,550 in drug spending this year (rising from $6,350 in 2020), except for very low-income beneficiaries.

Democrats and Republicans in Congress have proposed annual limits ranging from $2,000 to $3,100. But there’s disagreement about how to pay for that cost cap. Drug companies and insurers, which support the concept, want someone else to bear the financial burden.

That forces patients to rely on the financial assistance programs. These arrangements, however, do nothing to reduce prices. In fact, they help drive up America’s uniquely high drug spending by encouraging doctors and patients to use the priciest medications when cheaper alternatives may be available.

Growing Expense of Specialty, Cancer Medicines

Nearly 70% of seniors want Congress to pass an annual limit on out-of-pocket drug spending for Medicare beneficiaries, according to a KFF survey in 2019. (KHN is an editorially independent program of KFF.)

The affordability problem is worsened by soaring list prices for many specialty drugs used to treat cancer and other serious diseases. The out-of-pocket cost for Medicare and private insurance patients is often set as a percentage of the list price, as opposed to the lower rate negotiated by insurers.

For instance, prices for 54 orally administered cancer drugs shot up 40% from 2010 to 2018, averaging $167,904 for one year of treatment, according to a 2019 JAMA study. Bristol Myers Squibb, the manufacturer of Clark’s drug, Pomalyst, has raised the price 75% since it was approved in 2013, to about $237,000 a year. The company believes “pricing should be put in the context of the value, or benefit, the medicine delivers to patients, health care systems and society overall,” a spokesperson for Bristol Myers Squibb said via email.

As a result of rising prices, 1 million of the 46.5 million Part D drug plan enrollees spend above the program’s catastrophic coverage threshold and face $3,200 in average annual out-of-pocket costs, according to KFF. The hit is particularly heavy on cancer patients. In 2019, Part D enrollees’ average out-of-pocket cost for 11 orally administered cancer drugs was $10,470, according to the JAMA study.

The median annual income for Medicare beneficiaries is $26,000.

Medicare patients face modest out-of-pocket costs if their drugs are administered in the hospital or a doctor’s office and they have a Medigap or Medicare Advantage plan, which caps those expenses.

But during the past several years, dozens of effective drugs for cancer and other serious conditions have become available in oral form at the pharmacy. That means Medicare patients increasingly pay the Part D out-of-pocket costs with no set maximum.

“With the high cost of drugs today, that 5% can be a third or more of a patient’s Social Security check,” said Brian Connell, federal affairs director for the Leukemia & Lymphoma Society.

This has forced some older Americans to keep working, rather than retiring and going on Medicare, because their employer plan covers more of their drug costs. That way, they also can keep receiving financial help directly from drugmakers to pay for the costs not covered by their private plan, which isn’t allowed by Medicare.

‘This Is a Little Nuts’

All this has caused financial and emotional turmoil for people who face a life-threatening disease.

Marilyn Rose, who was diagnosed with chronic myeloid leukemia three years ago, until recently was paying nothing out-of-pocket for her cancer drug, Sprycel, which has a list price of $176,500 a year. That’s because Bristol Myers Squibb, the manufacturer, paid her insurance deductible and copays for the drug.

But the self-employed artist and designer, who lives in West Caldwell, New Jersey, recently turned 65 and went on Medicare. The Part D plan offering the best deal on Sprycel charges more than $10,000 a year in coinsurance for the drug.

Rose asked her oncologist if she could switch to an alternative medication, Gleevec, for which she’d pay just $445 a year. But she ultimately decided to stick with Sprycel, which her doctor said is a longer-lasting treatment. She hopes to qualify for financial aid from a foundation to cover the coinsurance but won’t know until sometime this month.

“It’s just strange you have to make a decision about your treatment based on your finances rather than what’s the right drug for you,” she said. “I always thought that when I get to Medicare age I’ll be able to breathe a sigh of relief. This is a little nuts.”

Bristol Myers Squibb paid Marilyn Rose’s insurance deductible and copays, so she could continue using Sprycel — a cancer drug for her leukemia — when she had private insurance. But Medicare doesn’t allow that. (Marilyn Rose)
Sharon Clark’s cancer drug, Pomalyst, costs her $18,000 for a 28-day supply. Patient assistance foundations provide financial aid, but to benefit she must be fortunate enough to catch the window for securing the limited funds available. (Sharon Clark)

Given the sticker shock, many other patients choose not to fill a needed prescription, or delay filling it. Nearly half of patients who face a price of $2,000 or more for a cancer drug walk away from the pharmacy without it, according to a 2017 study. Fewer than half of Medicare patients with blood cancer received treatment within 90 days of their diagnosis, according to a 2019 study commissioned by the Leukemia & Lymphoma Society.

“If I didn’t do really well at scrounging free drugs and getting copay foundations to work with us, my patients wouldn’t get the drug, which is awful,” said Dr. Barbara McAneny, an oncologist in Albuquerque, New Mexico, and past president of the American Medical Association. “Patients would just say, ‘I can’t afford it. I’ll just die.’”

The high drug prices and coverage gaps have forced many patients to rely on complicated financial assistance programs offered by drug companies and foundations. Under federal rules, the foundations can help Medicare patients as long as they pay for drugs made by all manufacturers, not just by the company funding the foundation.

But Daniel Klein, CEO of the PAN Foundation, which provides drug copay assistance to more than 100,000 people a year, said there are more patients in need than his foundation and others like it can help.

“If you are a normal consumer, you don’t know much about any of this until you get sick and all of a sudden you find out you can’t afford your medication,” he said. Patients are lucky, he added, if their doctor knows how to navigate the charitable assistance maze.

Yet many don’t. Daniel Sherman, who trains hospital staff members to navigate financial issues for patients, estimates that fewer than 5% of U.S. cancer centers have experts on staff to help patients with problems paying for their care.

Sharon Clark, who struggles to cover her cancer drugs, works with the Leukemia & Lymphoma Society counseling other patients on how to access helping resources. “People tell me they haven’t started treatment because they don’t have money to pay,” she said. “No one in this country should have to choose between housing, food or medicine. It should never be that way, never.”

This article is part of a series on the impact of high prescription drug costs on consumers made possible through the 2020 West Health and Families USA Media Fellowship.