The FDA's approval of Kisunla, a new monoclonal anti-amyloid Alzheimer's drug developed by Eli Lilly, is under scrutiny following a report in The BMJ highlighting substantial conflicts of interest among the physicians on the FDA's advisory committee. The investigation revealed that eight of the eleven members had received significant grants or consulting fees from Eli Lilly or other companies developing similar drugs.
Concerns Over Financial Ties
The BMJ investigation, conducted by Jeanne Lenzer and Shannon Brownlee, utilized the OpenPayments database and other sources to uncover the financial ties of the advisory committee members. It was found that advisors received up to $62,000 in payments for consulting and speaking fees, and held up to $10.5 million in research grants from companies developing anti-amyloid drugs. Specifically, three committee members had financial ties to Eli Lilly, and two to Roche, who is collaborating with Eli Lilly on Alzheimer's blood tests. Two members also held patents on other anti-amyloid drugs, and another received funding from Janssen for a different Alzheimer's drug.
Impact on Public Trust
Experts are raising concerns about the potential influence of these conflicts on the drug approval process and the public's perception of the FDA. Eric Widera, a geriatrician and professor of medicine at UCSF, stated that these financial conflicts of interest erode the public's faith in the FDA decisions. He fears that the FDA may be less inclined to include non-industry supported committee members who might challenge the agency's decisions.
Safety and Efficacy Questions
Despite Kisunla performing better than Aduhelm in clinical trials by slowing cognitive decline by a small amount, some experts question whether the benefits outweigh the risk of brain swelling and bleeding. The advisory committee unanimously recommended Kisunla's approval despite this uncertainty.
FDA's Response and Justification
The FDA does not consider most of these financial conflicts to be substantial and can issue waivers for potential committee members with significant conflicts if their expertise is deemed to outweigh the risk. Senior FDA regulators have justified the inclusion of committee members with financial conflicts, arguing that "experience that yields insights may create a potential COI [conflict of interest]."
Calls for Stricter Guidelines
Critics argue that even small payments can influence experts' decision-making. Widera suggests that stricter guidelines around financial conflicts of interest could bolster confidence in the agency, which already faces distrust from a significant portion of the American public. He notes that finding doctors without financial ties to drug companies is possible, as half of neurologists have no such ties.
Concerns Raised by Journalists
Independent journalists have also questioned the safety and effectiveness of Kisunla. A report in The BMJ raised concerns about deaths in people taking the drug and the financial ties of drug makers on the panel that approved the medication. Steven Goodman, an expert in clinical trial design at Stanford University, questioned the reliability of data provided by Lilly after the FDA's initial denial of approval, citing missing information and a failure to formally follow patients who stopped treatment due to adverse effects.
Alberto J. Espay, a neurologist and specialist in clinical epidemiology and healthcare research at the University of Cincinnati, criticized Lilly's promotion of donanemab, stating that the claimed 35% slowing of decline is a misleading relative difference that transforms a very tiny absolute difference into a number that seems impressive.
