Biogen’s closely watched experimental medicine for Alzheimer’s disease has generated “insufficient” evidence to conclude that it would help patients, according to a withering assessment from an influential drug-pricing watchdog group that comes four weeks before regulators decide whether to approve it.
Citing conflicting results from two late-stage clinical trials and indications that the medicine, called aducanumab, can cause worrisome side effects, the Boston-based group said in a draft report Wednesday that the Cambridge firm’s drug would deserve an annual price tag of $2,500 to $8,300 if approved, given its modest benefits.
That’s a fraction of the $50,000 some analysts had predicted aducanumab would command if the Food and Drug Administration signs off on it. The FDA hasn’t cleared a new Alzheimer’s drug since 2003, and those on the market provide only marginal benefits. A medicine that halts or reverses the devastating form of dementia, particularly early in its onset, would be a blockbuster ― defined as annual sales of at least $1 billion ― and give hope to millions of Americans affected by the disease.
Unfortunately, aducanumab doesn’t appear to be that drug, according to the Institute for Clinical and Economic Review, or ICER.
“Nearly everyone has been touched by Alzheimer’s disease through its effects on family members, friends, colleagues or themselves,” Dr. David Rind, ICER’s chief medical officer, said in a news release accompanying the report. “It is a condition that people dread like no other, and the first therapy that effectively cures or stops the progression of the disease will warrant a very high price in the US health system.
But, he said, ICER experts who studied clinical trial results and other data concluded that “evidence remains insufficient to determine whether the drug provides an overall health benefit.”
The densely written 123-page report is only a “preliminary draft” that marks the midpoint of the institute’s review process. The group plans to solicit public comment and issue a revised report on June 30, about three weeks after the FDA is expected to rule.
Nonetheless, the draft report will only increase doubts about aducanumab, whose ups and downs over the past couple of years have swung billions of dollars on the stock market, raising and then dashing the hopes of patients and their loved ones. ICER has no regulatory authority, but the 15-year-old nonprofit has gained clout as it has publicly pressured drug companies to charge only what medicines are worth.
Biogen, which developed the drug with its Japanese partner, Eisai, said in a statement that the draft report “does not accurately reflect the possible holistic value” of aducanumab. “It does not factor in Alzheimer’s disease’s massive burden on society and misses the mark on how much strain is placed on families who care for their loved ones,” Biogen said.
The company also said that ICER has assessed the value of drugs 102 times since 2016 and only 12 times found the medicines to be priced appropriately. Overall, the group recommended a median price cut of 50 percent, Biogen said.
Aducanumab is a monoclonal antibody made from the immune cells of older people with no or uncommonly slow cognitive decline. Researchers designed it to remove a sticky substance from the brain called beta amyloid that some believe contributes to Alzheimer’s disease, although other researchers challenge that theory.
In contrast to older Alzheimer’s drugs such as Namenda and Aricept, which come in pill form, aducanumab would be administered intravenously for about an hour every four weeks.
Biogen ran two late-stage trials that contradicted each other on whether the drug slowed or halted cognitive decline. Flummoxed, ICER averaged the results, even though Rind said in an interview that “it’s unlikely that the truth lies at the average of these two trials.”
Adding to the watchdog group’s concerns were the number of aducanumab recipients in the trials who experienced a side effect known as ARIA, an inflammation of the brain that can range from mild and manageable to fatal if not controlled. More than 40 percent of recipients experienced some form of ARIA, Rind said, although most cases were asymptomatic.
“We’re sure that the drug has harmful side effects,” said Rind, who has practiced medicine for 30 years at Beth Israel Deaconess Medical Center. “That doesn’t mean that if it works, it’s not worth taking. But if it doesn’t work, all you’re getting are the harmful side effects.”
In recent years, ICER has drawn fire from drug companies and other critics over how it calculates the value of drugs. The Pioneer Institute, a libertarian-leaning think tank, said in 2019 that the group uses a “one-size-fits-all” approach to determine fair prices for prescription drugs, a mind-set particularly ill-suited for a growing wave of expensive medicines that treat rare diseases.
But ICER has found that some drugs with jaw-dropping prices are worth it, including Zolgensma, a revolutionary gene therapy for a rare genetic disease called spinal muscular atrophy. The Swiss drug giant Novartis priced the life-saving, one-time treatment at $2.1 million in 2019. The watchdog group said it was reasonable given how much Zolgensma could save the health care system in hospitalizations and other costs.
Biogen, which specializes in medicines for neurological diseases and has the largest workforce of any drug firm based in Massachusetts ― about 2,400 employees ― has been working on aducanumab for years. People following the drug have been whipsawed by its changing fortunes.
In March 2019, Biogen abruptly ended a pivotal trial of aducanumab after an early look at results indicated it did not provide a significant benefit. The news sent Biogen stock into a freefall, with the firm losing a staggering $18 billion of its value in a single day.
Seven months later, the biotech stunned many by reversing itself and saying it had decided to seek FDA approval after all. Biogen executives said their initial conclusion was wrong and that a look at a larger set of data revealed that patients treated with the drug showed improvements in memory, orientation, and language.
Last November, before an 11-member advisory panel met to consider the drug, the FDA posted background documents on its website with glowing reviews of aducanumab. Biogen’s share price soared nearly 44 percent. But the stock plunged days later after the advisory panel said Biogen had failed to prove the medicine was effective and had cherry-picked positive clinical trial data and jettisoned negative results.
The FDA initially said it would decide whether to approve aducanumab in March. But the agency pushed that back until June 7. Analysts reading the tea leaves have said the delay could portend good or bad news.
As many as 5.8 million Americans were living with Alzheimer’s disease last year, according to the Centers for Disease Control and Prevention. That number is projected to nearly triple to 14 million people by 2060.
Jonathan Saltzman can be reached at firstname.lastname@example.org.