UP­DAT­ED: CMS to re­strict cov­er­age of Bio­gen's con­tro­ver­sial Alzheimer's drug to on­ly clin­i­cal tri­als

The Cen­ters for Medicare and Med­ic­aid Ser­vices on Tues­day said it will on­ly pay for Bio­gen’s Aduhelm and oth­er FDA-ap­proved an­ti-amy­loid mon­o­clon­al an­ti­bod­ies for Alzheimer’s dis­ease un­der CMS-ap­proved ran­dom­ized con­trolled tri­als.

The draft na­tion­al cov­er­age de­ci­sion, which in­sur­ers na­tion­wide are like­ly to fol­low, makes clear that CMS will be look­ing for ran­dom­ized con­trolled tri­als that “demon­strate a clin­i­cal­ly mean­ing­ful ben­e­fit in cog­ni­tion and func­tion.” That will be a tough task for Bio­gen, which pre­vi­ous­ly showed con­flict­ing ben­e­fits from past Aduhelm tri­als that were ini­tial­ly cut short due to fu­til­i­ty and then res­ur­rect­ed for the ac­cel­er­at­ed ap­proval.

“None of the tri­als com­plet­ed as of the pub­li­ca­tion of this NCA has con­vinc­ing­ly demon­strat­ed that use of an­ti­amy­loid mAbs re­sult in a mean­ing­ful im­prove­ment in health out­comes for AD pa­tients,” CMS said in its draft de­ci­sion, which is now open for 30 days of more com­ments, and will be fi­nal­ized in April.

Hol­ly Fer­nan­dez Lynch, a bioethics pro­fes­sor at the Uni­ver­si­ty of Penn­syl­va­nia, told End­points News that she thinks CMS made the right de­ci­sion in go­ing for cov­er­age with ev­i­dence de­vel­op­ment (CED) and re­quir­ing the tri­al, al­though she not­ed how odd it is that the gov­ern­ment will be es­sen­tial­ly pay­ing Bio­gen to run a tri­al.

“I didn’t think out­right re­fusal of any cov­er­age was gen­uine­ly on the ta­ble. This is a pret­ty strong re­buke of FDA as it is,” she said.

The an­nounce­ment is a blow for Bio­gen, which will like­ly have to de­sign and run an­oth­er clin­i­cal tri­al in ad­di­tion to its con­fir­ma­to­ry tri­al to sat­is­fy the FDA’s ac­cel­er­at­ed ap­proval re­quire­ments. Bio­gen’s stock dropped about 8% Tues­day af­ter­noon.

“This draft cov­er­age de­ter­mi­na­tion de­nies the dai­ly bur­den of peo­ple liv­ing with Alzheimer’s dis­ease,” Bio­gen said in a state­ment emailed to End­points, adding:

Cov­er­age with ev­i­dence de­vel­op­ment (CED) un­der a ran­dom­ized clin­i­cal tri­al will ex­clude al­most all pa­tients who may ben­e­fit. This will sig­nif­i­cant­ly lim­it pa­tient ac­cess to an FDA-ap­proved treat­ment, es­pe­cial­ly for un­der­served pa­tients as ev­i­denced in oth­er CED de­ter­mi­na­tions. CEDs can take months to years to ini­ti­ate, and hun­dreds of Alzheimer’s pa­tients – the ma­jor­i­ty of whom are Medicare ben­e­fi­cia­ries – are pro­gress­ing each day from mild to mod­er­ate dis­ease stages, where treat­ment may no longer be an op­tion.

But Lon Schnei­der, who di­rects the Uni­ver­si­ty of South­ern Cal­i­for­nia’s State of Cal­i­for­nia Alzheimer’s Dis­ease Cen­ter, told End­points that 80% of pa­tients in the Bio­gen tri­als had pro­dro­mal AD, which is “de­f­i­n­i­tion­al­ly, vir­tu­al­ly no dai­ly bur­den (a bit of mem­o­ry im­pair­ment, yes, a bit of amy­loid? Yes). And the tri­als couldn’t demon­strate that any one pa­tient ben­e­fit­ted from ad­u­canum­ab, so who’s be­ing de­prived ben­e­fit?”

He called the move “a smack­down” as CMS “al­so told Lil­ly that FDA might give you AA [ac­cel­er­at­ed ap­proval] or BTD [break­through des­ig­na­tion] but we’ll wait to see pos­i­tive tri­als re­sults.”

In­dus­try group PhRMA of­fered a sim­i­lar char­ac­ter­i­za­tion, not­ing, “With this pro­pos­al, CMS is writ­ing off an en­tire class of med­i­cines be­fore mul­ti­ple prod­ucts have even been re­viewed by FDA, po­si­tion­ing it­self and not FDA as the key ar­biter of clin­i­cal ev­i­dence.”

The FDA de­clined to com­ment on the de­ci­sion by CMS.

CMS al­so lays out very spe­cif­ic tri­al re­quire­ments that Bio­gen, Roche, Eli Lil­ly and any oth­er amy­loid con­tenders will have to meet, which is not what CMS has done in pre­vi­ous na­tion­al cov­er­age de­ci­sions, not­ing that it’s aware of at least three oth­er an­ti-amy­loid mAbs cur­rent­ly ap­proach­ing Phase 3 tri­als.

“The di­ver­si­ty of pa­tients in­clud­ed in each tri­al must be rep­re­sen­ta­tive of the na­tion­al pop­u­la­tion di­ag­nosed with AD,” CMS says, not­ing that the tri­als must ad­dress, “at a min­i­mum,” whether the  use of mAbs di­rect­ed against amy­loid re­sult in a sta­tis­ti­cal­ly sig­nif­i­cant and clin­i­cal­ly mean­ing­ful dif­fer­ence in de­cline in cog­ni­tion and func­tion, and whether they ad­dress the ad­verse events as­so­ci­at­ed with the use of these an­ti-amy­loid mAbs.

The news comes as Bio­gen re­cent­ly cut Aduhelm’s price in half, af­ter sell­ing just $300,000 of Aduhelm in the ear­ly months, and com­ing un­der heavy crit­i­cism for the $56,000 price tag that forced CMS to prep for record-high pre­mi­um in­creas­es for se­niors. HHS Sec­re­tary Xavier Be­cer­ra ear­li­er this week called on CMS to re­con­sid­er those steep pre­mi­um in­creas­es now that Aduhelm’s price has been re­duced.

Sen. Bernie Sanders of Ver­mont said in a state­ment that CMS’ de­ci­sion “is an im­por­tant step for­ward, es­pe­cial­ly fol­low­ing Sec­re­tary Be­cer­ra’s move yes­ter­day to di­rect Medicare to re­con­sid­er a pre­mi­um rate hike caused in part by the out­ra­geous price of Aduhelm.”

Oth­ers who be­lieve that Aduhelm does work were dis­ap­point­ed by the de­ci­sion from CMS, which will like­ly mean on­ly a lim­it­ed num­ber of pa­tients are cov­ered un­der a CMS-ap­proved clin­i­cal tri­al.

“This is clear­ly dis­ap­point­ing news, as CED would sig­nif­i­cant­ly lim­it the num­ber of pa­tients who can ac­cess Aduhelm and oth­er an­ti-Abe­ta mAbs, and in this sce­nario, we would ex­pect a pro­longed process to ini­ti­ate and en­roll pa­tients in­to the CED clin­i­cal tri­als which need to be re­viewed and ap­proved by CMS,” SVB Leerink told in­vestors.

Ad­vo­ca­cy or­ga­ni­za­tions were sim­i­lar­ly not pleased.

Har­ry Johns, Alzheimer’s As­so­ci­a­tion CEO, said in a state­ment, “To­day’s draft de­ci­sion by the Cen­ters for Medicare & Med­ic­aid Ser­vices (CMS) is shock­ing dis­crim­i­na­tion against every­one with Alzheimer’s dis­ease, es­pe­cial­ly those who are al­ready dis­pro­por­tion­ate­ly im­pact­ed by this fa­tal dis­ease, in­clud­ing women, Blacks and His­pan­ics.”

George Vraden­burg, chair and co-founder of Us­Again­stAlzheimer’s, added, “This is ab­solute­ly un­ac­cept­able. If this de­ci­sion stands, for the first time in his­to­ry, mil­lions of Amer­i­cans will be de­nied cov­er­age not just to a drug, but to a whole class of drugs—not by the agency that reg­u­lates drugs but by the fed­er­al in­sur­ance bu­reau­cra­cy.”

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with ad­di­tion­al com­ments.

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