“阿尔茨海默病之光”获批背后有猫腻？

A truly strange thing happened on July 8: Pharma giant Biogen, maker of the pioneering and highly controversial Alzheimer's drug Aduhelm (also called by its scientific name aducanumab), voluntarily hacked away at its own market reach by requesting that the Food and Drug Administration (FDA) cut back on the drug's prescribing label.

The agency, which had essentially approved Aduhelm for the vast majority of Alzheimer's patients, granted the request (although some details and official changes still need to be hammered out), wherein Biogen emphasized that Aduhelm should be initially funneled to patients with mild cognitive impairment or mild dementia since those were the kinds of patients involved in the clinical studies leading to the aducanumab approval. It should be noted that it's unclear whether the FDA or Biogen initiated the label changing process, but the end result is the same.

Drug giants don't typically cut off billions in potential revenues from a landmark treatment voluntarily, although the company could still reap massive financial gains from Aduhelm, given its hefty price tag and Alzheimer's prevalence in America. But nothing in the messy path to Aduhelm's approval and the fierce scrutiny it has elicited is exactly normal. And, even with the prescribing label change, things may soon become very awkward between doctors and their patients who are seeking Biogen's therapy.

A new survey conducted by Medscape, a health care-focused publication which caters to the medical profession, finds that an overwhelming number of physicians, including 89% of neurologists, either disagree or strongly disagree with the FDA's decision to approve Aduhelm despite little-to-no proof of its efficacy in slowing cognitive decline in Alzheimer's patients. And that means families clinging to the hope of finally having an available treatment that addresses the underlying disease of Alzheimer's, rather than just its symptoms, could be in for some tough conversations with doctors reluctant to prescribe it.

The fact that the FDA delivered a wide-ranging drug approval for a disease which is among the leading causes of death in America despite the agency's own expert independent panels' strong disapproval certainly hasn't quelled the political firestorm facing the regulatory body, July 8's label change announcement aside. Neither has Biogen's decision to set a yearly list price of $56,000 on aducanumab, which could cost public health programs such as Medicare $57 billion in a single year if just one million beneficiaries were to receive it. Plus, Biogen has only committed to four years of a moratorium on Aduhelm price increases even though it has close to a decade to demonstrate whether its now-approved treatment actually works in a real-world setting.

That series of dramatic events seems to be swirling in physicians' heads, per Medscape's survey. But the biggest issue appears to be whether or not it's justifiable to prescribe Alzheimer's patients a pricey treatment like Aduhelm only to give their families and caretakers false hope if it winds up flopping on a practical level. Some 60% of the physicians who responded to the poll said Biogen's data was unclear in establishing a clear clinical benefit for patients. And 79% of American physicians and 68% of neurologists who were surveyed say they don't plan to prescribe aducanumab to their Alzheimer's patients.

The seeming reticence among the U.S. medical class may eventually give way to patient advocacy pressure, which was largely credited with Aduhelm's unlikely approval as well. But Congress has already taken note of the growing controversy and the likes of Sen. Joe Manchin of West Virginia and Reps. Frank Pallone, Carolyn Maloney, and Katie Porter of New Jersey, New York, and California, respectively, have called for greater scrutiny of the FDA. That could lead to a public cry for a shakeup of FDA leadership, as Manchin has done, and an examination of what some watchdogs say has been a cozy relationship between the agency and the pharmaceutical industry it's charged with regulating.

"Our Committees will be investigating this matter so Congress and the American people can better understand why this drug was approved, how Biogen set its price and what impact this will have on research for future Alzheimer’s treatments and federal health care programs," wrote Reps. Maloney and Pallone, chairs of the respective House Oversight and Reform Committee and Energy and Commerce Committee, in a statement in June.

Porter, who is known for her hard-nosed examinations of Congressional witnesses including Big Pharma executives, jumped into the fray on July 6 by calling for an independent investigation of how FDA officials interact with pharma companies like Biogen.

Patients should have confidence that their treatment plans are based on science, not cozy relationships between Big Pharma and @US_FDA officials. I'm concerned the approval process for certain drugs has been compromised, so I'm urging an independent watchdog to investigate. pic.twitter.com/LgLzcIGVnN

Porter specifically points to the so-called "Project Onyx," an alleged effort by Biogen to lobby top FDA officials to get Aduhelm — a drug the company's own independent safety monitoring board for clinical trials deemed "futile — across the regulatory finish line. A report by STAT News points to multiple off-the-record and back channel meetings between Biogen and senior FDA staff who appeared determined to get Aduhelm to the market.

Aducanumab's financial and regulatory future is still up in the air. But between the skepticism of physicians and the wrath of politicians, the messiness of the process leading to this ostensible Alzheimer's breakthrough's approval is breeding some chaos.