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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; and more

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Clay Siegall, Morphimmune CEO

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Eu­ro­pean doc­tors di­al up dig­i­tal com­mu­ni­ca­tion with phar­mas, but still lean to­ward in-per­son med meet­ings, study finds

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Judge al­lows ex­pert tes­ti­mo­ny in GSK tri­al al­leg­ing Zan­tac link to can­cer

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