Alzheimer’s & Dementia researchers challenge FDA’s approval of Aduhelm given lack of evidence for beta-amyloid as a marker

by

Doc­tors Blast Bio­gen Alzheimer Approval as ‘Reg­u­la­to­ry Fail­ure’ (Bloomberg):

Top researchers who advised the U.S. Food and Drug Admin­is­tra­tion on Bio­gen Inc.’s Alzheimer’s drug blast­ed the agency for approv­ing it, call­ing the deci­sion a “reg­u­la­to­ry fail­ure” that is “at odds with the evidence.”

The New Eng­land Jour­nal of Med­i­cine opin­ion piece, signed by sev­en mem­bers of an advi­so­ry pan­el that opposed clear­ing Biogen’s Aduhelm, is anoth­er sign of per­sis­tent furor over the agency’s deci­sion … The new com­men­tary is signed by them and four oth­er pan­el mem­bers, includ­ing doc­tors from Har­vard Med­ical School, the Mayo Clin­ic, and the Uni­ver­si­ty of Cal­i­for­nia, San Francisco.

An inves­ti­ga­tion of Aduhelm’s approval “should be expe­di­tious­ly per­formed, so as to learn how this reg­u­la­to­ry fail­ure occurred and to ensure that it doesn’t occur again,” the researchers wrote.

The Statement:

Revis­it­ing FDA Approval of Adu­canum­ab (oped at The New Eng­land Jour­nal of Medicine)

The com­mit­tee was nev­er con­sult­ed about beta-amyloid’s suit­abil­i­ty as a sur­ro­gate. Indeed, the lead FDA sci­en­tist told us, “We’re not using the amy­loid as a sur­ro­gate for effi­ca­cy.” More­over, the data did not sup­port this use. An effec­tive sur­ro­gate should strong­ly cor­re­late with a clin­i­cal end point in clin­i­cal stud­ies, but an FDA sta­tis­ti­cal review of Stud­ies 301 and 302 found no evi­dence that amy­loid changes cor­re­lat­ed with cog­ni­tive or func­tion­al changes, con­clud­ing that “it is not clear that there is any link­age between reduc­tion in plaque and long term clin­i­cal change” …

The FDA’s deci­sion is at odds with the evi­dence and with the agency’s bio­sta­tis­ti­cal review. The over­whelm­ing unmet need in this com­mon and dev­as­tat­ing dis­ease should dri­ve research invest­ments, not low­er­ing of reg­u­la­to­ry stan­dards that Amer­i­cans rely on for safe and effec­tive med­i­cines. The FDA has released key inter­nal reviews, but they nei­ther pro­vide a per­sua­sive sci­en­tif­ic basis for declar­ing beta-amy­loid a rea­son­able sur­ro­gate nor jus­ti­fy the fail­ure to seek advi­so­ry-com­mit­tee input on this impor­tant ques­tion. The inter­im FDA Commissioner’s deci­sion to call for an Office of the Inspec­tor Gen­er­al inves­ti­ga­tion is appro­pri­ate, and we believe such an inves­ti­ga­tion should be expe­di­tious­ly per­formed, so as to learn how this reg­u­la­to­ry fail­ure occurred and to ensure that it doesn’t occur again. Though the deci­sion will rever­ber­ate for years, ear­ly signs of its grav­i­ty are already reflect­ed in announce­ments by two oth­er man­u­fac­tur­ers that they will seek accel­er­at­ed approval for Alzheimer’s treat­ments on the basis of amy­loid as a surrogate.

News in Context: