UP­DAT­ED: CMS fi­nal­izes re­stric­tions on Bio­gen's Alzheimer's drug cov­er­age, will on­ly fund use in clin­i­cal tri­als

CMS late Thurs­day fi­nal­ized its de­ci­sion to re­strict cov­er­age for Bio­gen’s con­tro­ver­sial Alzheimer’s drug Aduhelm and oth­er amy­loid-tar­get­ed drugs to just pa­tients par­tic­i­pat­ing in clin­i­cal tri­als.

“Mon­o­clon­al an­ti­bod­ies di­rect­ed against amy­loid that are ap­proved by FDA for the treat­ment of AD [Alzheimer’s dis­ease] based up­on ev­i­dence of ef­fi­ca­cy from a change in a sur­ro­gate end­point (e.g., amy­loid re­duc­tion) con­sid­ered as rea­son­ably like­ly to pre­dict clin­i­cal ben­e­fit may be cov­ered in a ran­dom­ized con­trolled tri­al con­duct­ed un­der an in­ves­ti­ga­tion­al new drug (IND) ap­pli­ca­tion,” CMS said in its fi­nal de­ci­sion sum­ma­ry.

While rec­og­niz­ing the rar­i­ty of this de­ci­sion, in that it’s re­quir­ing a ran­dom­ized con­trolled tri­al, CMS said it has fi­nal­ized past Na­tion­al Cov­er­age De­ter­mi­na­tions for drugs/bi­o­log­ics with CED but nev­er with an RCT.

And it stressed that de­spite the FDA’s ac­cel­er­at­ed ap­proval for Aduhelm, “cur­rent­ly no Alzheimer’s drug of any type has suc­ceed­ed, to date, in mod­i­fy­ing dis­ease pro­gres­sion. No tri­al in­volv­ing any in­ter­ven­tion, alone or com­bined, has yet demon­strat­ed a mean­ing­ful im­prove­ment in health out­comes for pa­tients treat­ed with an­ti-amy­loid mAbs for the treat­ment of AD.”

The de­ci­sion comes as Roche and Eli Lil­ly (CMS called the Phase II tri­al of do­nanemab “promis­ing”) are al­so ad­vanc­ing their own amy­loid-tar­get­ed drugs through late-stage tri­als, with read­outs ex­pect­ed lat­er this year, and high hopes, at least for Lil­ly, for a sim­i­lar ac­cel­er­at­ed ap­proval. Mean­while, the de­ci­sion from CMS al­so shows the lim­its of a fer­vent push among in­dus­try-backed Alzheimer’s ad­vo­cates on Capi­tol Hill to re­verse CMS’ ear­li­er draft de­ci­sion that laid out these cov­er­age con­straints.

CMS re­ceived over 10,000 com­ments on that draft, ex­plain­ing on Thurs­day that, “None of the com­ments in­clud­ed new ev­i­dence that met our in­clu­sion/ex­clu­sion cri­te­ria. How­ev­er, Bio­gen’s re­cent pub­li­ca­tion of its EMERGE and EN­GAGE tri­al re­sults was re­viewed as well as the new Amer­i­can Acad­e­my of Neu­rol­o­gy (AAN) guide­lines.”

In re­sponse to the “ma­jor­i­ty of pub­lic com­ments” say­ing “that there is not enough ev­i­dence show­ing that these drugs/bi­o­log­i­cals pro­vide a clin­i­cal ben­e­fit in or­der to cov­er an­ti-amy­loid mAbs,” CMS said it “be­lieves that the CED as mod­i­fied in this fi­nal de­ci­sion is the right bal­ance of pro­vid­ing ap­pro­pri­ate pa­tient ac­cess and pa­tient pro­tec­tions as well as gen­er­at­ing ev­i­dence need­ed for pa­tients, clin­i­cians and care­givers.”

Part of that mod­i­fi­ca­tion means that CMS will not re­quire a sep­a­rate ran­dom­ized con­trolled tri­al that du­pli­cates an RCT con­duct­ed for the FDA’s ac­cel­er­at­ed ap­proval, and which Bio­gen al­ready agreed on a pro­to­col for.

“We re­moved the ‘CMS-ap­proved tri­al’ lan­guage to fur­ther avoid any con­fu­sion with re­gard to CMS’ in­tent to sup­port FDA re­quired RCTs,” the agency says. But the fi­nal NCD al­so goes a step fur­ther and says that at this time,

CMS be­lieves an FDA de­ter­mi­na­tion of a drug/bi­o­log­ic that demon­strates ef­fi­ca­cy from a di­rect mea­sure of clin­i­cal ben­e­fit would be promis­ing but would not meet the 1862(a)(1)(A) rea­son­able and nec­es­sary statute. A prospec­tive com­par­a­tive study, which could range from a reg­istry with a com­para­tor to a prag­mat­ic clin­i­cal study is ap­pro­pri­ate cov­er­age un­til CMS knows that the drug/bi­o­log­ic will demon­strate the same health out­comes, with rea­son­able risk of harm in broad com­mu­ni­ty prac­tice.

SVB Leerink an­a­lysts ex­plained in an in­vestor note Thurs­day how for mAbs that get tra­di­tion­al ap­proval (which Roche is go­ing for) based on di­rect mea­sure­ments of clin­i­cal ben­e­fit, “CMS would pro­vide en­hanced ac­cess and cov­er­age in CMS-ap­proved prospec­tive com­par­a­tive stud­ies, such as a da­ta col­lec­tion through rou­tine clin­i­cal prac­tice or reg­istries. And these prod­ucts could be cov­ered in ad­di­tion­al care set­tings, such as an out­pa­tient de­part­ment or an in­fu­sion cen­ter.”

The de­ci­sion caps a tu­mul­tuous run for Bio­gen that be­gan with an un­ex­pect­ed ac­cel­er­at­ed ap­proval and ex­pec­ta­tions for tens of bil­lions in sales, but end­ed with a fight over this CMS de­ci­sion, sig­nif­i­cant lay­offs and now lim­it­ed cov­er­age from CMS like­ly lead­ing to con­tin­ued ane­mic Aduhelm sales, po­ten­tial­ly un­til the com­pa­ny can com­plete its con­fir­ma­to­ry tri­al in about four years.

“Med­ical in­no­va­tion must in­clude clin­i­cal tri­als that demon­strate ben­e­fit to pa­tients,” CMS said in its de­ci­sion memo. “Con­verse­ly, cov­er­ing a drug that has not been shown to be ef­fec­tive may in­cen­tivize pro­duc­tion, mar­ket­ing and sales of sim­i­lar­ly in­ef­fec­tive drugs, at the cost of hard re­search to find ones that do pro­vide a clin­i­cal ben­e­fit to pa­tients.”

Bio­gen said in a state­ment:

These cov­er­age re­stric­tions, in­clud­ing the dis­tinc­tion be­tween ac­cel­er­at­ed ap­proval and tra­di­tion­al ap­proval, have nev­er been ap­plied to FDA-ap­proved med­i­cines for oth­er dis­ease ar­eas….Bio­gen is care­ful­ly con­sid­er­ing its op­tions and will pro­vide up­dates as the com­pa­ny fur­ther eval­u­ates the busi­ness im­pact of this de­ci­sion.

Albert Bourla, Pfizer CEO (John Thys/POOL/AFP via Getty Images)

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Sanofi's new headquarters, La Maison Sanofi, in Paris (Credit: Luc Boegly)

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Tom Riga, Spectrum Pharmaceuticals CEO

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Merck targets vaccine-hesitant parents in its latest 'Why Vaccines' campaign. (Image: Shutterstock)

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Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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