Growing backlash against the FDA approval of unproven Alzheimer’s treatment Aduhelm, by Biogen

ICER Issues State­ment on the FDA’s Approval of Adu­canum­ab for Alzheimer’s Dis­ease (Insti­tute for Clin­i­cal and Eco­nom­ic Review):

The Insti­tute for Clin­i­cal and Eco­nom­ic Review (ICER) believes that the FDA, in approv­ing adu­canum­ab (Aduhelm™, Bio­gen) for the treat­ment of Alzheimer’s dis­ease, has failed in its respon­si­bil­i­ty to pro­tect patients and fam­i­lies from unproven treat­ments with known harms.

Our review of the evi­dence was con­cor­dant with that of many inde­pen­dent experts: cur­rent evi­dence is insuf­fi­cient to demon­strate that adu­canum­ab ben­e­fits patients. The avenue for­ward has seemed clear: anoth­er study would be need­ed to reduce the sub­stan­tial uncer­tain­ty about the drug’s effec­tive­ness, a require­ment of even greater pri­or­i­ty because of the drug’s com­mon and poten­tial­ly seri­ous side effects.

How­ev­er, instead of wait­ing for such a tri­al, the FDA chose to move the goal­posts and approve adu­canum­ab based on the sur­ro­gate out­come of remov­ing amy­loid from the brain rather than the patient-cen­tered out­come of clin­i­cal ben­e­fit, which has been required of all pre­vi­ous emerg­ing treat­ments for Alzheimer’s dis­ease. Many oth­er drugs have been shown to remove amy­loid from the brain, yet have failed to help patients, mak­ing this deci­sion all the more puz­zling. Keep read­ing the impor­tant state­ment HERE, over at ICER website.

The Announcement:

FDA Grants Accel­er­at­ed Approval for Alzheimer’s Drug (press release):

Today, the U.S. Food and Drug Admin­is­tra­tion approved Aduhelm (adu­canum­ab) for the treat­ment of Alzheimer’s, a debil­i­tat­ing dis­ease affect­ing 6.2 mil­lion Amer­i­cans. Aduhelm was approved using the accel­er­at­ed approval path­way, which can be used for a drug for a seri­ous or life-threat­en­ing ill­ness that pro­vides a mean­ing­ful ther­a­peu­tic advan­tage over exist­ing treat­ments. Accel­er­at­ed approval can be based on the drug’s effect on a sur­ro­gate end­point that is rea­son­ably like­ly to pre­dict a clin­i­cal ben­e­fit to patients, with a required post-approval tri­al to ver­i­fy that the drug pro­vides the expect­ed clin­i­cal ben­e­fit … Alzheimer’s is an irre­versible, pro­gres­sive brain dis­or­der that slow­ly destroys mem­o­ry and think­ing skills, and even­tu­al­ly, the abil­i­ty to car­ry out sim­ple tasks. While the spe­cif­ic caus­es of Alzheimer’s dis­ease are not ful­ly known, it is char­ac­ter­ized by changes in the brain—including amy­loid plaques and neu­rofib­ril­lary, or tau, tangles—that result in loss of neu­rons and their con­nec­tions. These changes affect a person’s abil­i­ty to remem­ber and think.

… The pre­scrib­ing infor­ma­tion for Aduhelm includes a warn­ing for amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA), which most com­mon­ly presents as tem­po­rary swelling in areas of the brain that usu­al­ly resolves over time and does not cause symp­toms, though some peo­ple may have symp­toms such as headache, con­fu­sion, dizzi­ness, vision changes, or nau­sea. Anoth­er warn­ing for Aduhelm is for a risk of hyper­sen­si­tiv­i­ty reac­tions, includ­ing angioede­ma and urticaria. The most com­mon side effects of Aduhelm were ARIA, headache, fall, diar­rhea, and confusion/delirium/altered men­tal status/disorientation.

Under the accel­er­at­ed approval pro­vi­sions, which pro­vide patients suf­fer­ing from the dis­ease ear­li­er access to the treat­ment, the FDA is requir­ing the com­pa­ny, Bio­gen, to con­duct a new ran­dom­ized, con­trolled clin­i­cal tri­al to ver­i­fy the drug’s clin­i­cal ben­e­fit. If the tri­al fails to ver­i­fy clin­i­cal ben­e­fit, the FDA may ini­ti­ate pro­ceed­ings to with­draw approval of the drug.

News in Context:

• Three mem­bers of the FDA advi­so­ry com­mit­tee have already resigned in protest. Here’s their rea­son­ing: Joel Perl­mut­ter, David Knop­man and Aaron Kessel­heim.
• What does a clear major­i­ty of the bio­phar­ma indus­try think of the FDA approval of adu­canum­ab? ‘Hor­ri­fy­ing’ ‘Dan­ger­ous’ ‘Con­fus­ing’ ‘Dis­as­ter’
• ‘Sim­ply unac­cept­able’: Alzheimer’s Asso­ci­a­tion blasts Bio­gen over the price of its new medicine
• Study chal­lenges the “seduc­tive” amy­loid hypoth­e­sis of Alzheimer’s dis­ease (AD)
• Brain scans show low­er accu­mu­la­tion of tau and amy­loid pathol­o­gy among cog­ni­tive “super-agers”
• Cog­ni­tive train­ing, diet, exer­cise, and vas­cu­lar man­age­ment seen to improve cog­ni­tion even in peo­ple with genet­ic pre­dis­po­si­tion for demen­tia (APOE e4)
• Report: 35% of world­wide demen­tia cas­es could be pre­vent­ed by mod­i­fy­ing these 9 mod­i­fi­able risk factors
• From Wikipedia: On Jan­u­ary 27, 2021 a coali­tion of 28 pub­lic health groups and opi­oid cri­sis orga­ni­za­tions sent a let­ter to the Biden Admin­is­tra­tion regard­ing Wood­cock­’s posi­tion as Act­ing Com­mis­sion­er of the FDA. The let­ter said in part that “as the Direc­tor of the FDA’s Cen­ter for Drug Eval­u­a­tion and Research (CDER) for more than 25 years, Dr. Wood­cock presided over one of the worst reg­u­la­to­ry agency fail­ures in U.S. his­to­ry.”^[Exam­ples of improp­er opi­oid deci­sions men­tioned in the let­ter include “approv­ing Opana with­out ade­quate evi­dence of safe­ty or long-term effi­ca­cy, approv­ing Zohy­dro despite a vote of 11–2 against approval by a sci­en­tif­ic advi­so­ry com­mit­tee, and approv­ing pro­mo­tion of Oxy­Con­tin for chil­dren as young as 11 years old.”