Endpoints News
Thank you for reading!
basic
UPGRADE
Wednesday
7 June, 2023
spotlight
in focus
top stories
1. FDA signals likely full approval for Eisai's new Alzheimer's drug ahead of Friday's adcomm
2. Updated: FDA pulls paid Eisai consultant from temporary role on adcomm reviewing Eisai's new Alzheimer's drug
3. CMS makes it official: Coverage for new Alzheimer's drugs once full approvals arrive
4. FDA commissioner says drug prices are too high, calls for better evidence generation
5. Merck sues US government over IRA, challenging drug pricing bill’s constitutionality
6. Merck sued the US to block the drug pricing law. Will other pharma companies follow suit?
7. FDA to import versions of common cancer drug to alleviate shortage
8. Senator Ron Wyden presses FDA and DEA on generic Adderall shortage
9. FDA lifts clinical hold on Foghorn’s study for blood and bone marrow cancer treatment
10. FDA lifts hold on Molecular Templates’ multiple myeloma trial after less than two months
more stories
 
Zachary Brennan
.

As we gear up for Friday's advisory committee hearing to review the confirmatory trial for Eisai's new Alzheimer's drug Leqembi, it's hard not to look at the draft committee roster, with just 6 voting members, and wonder why there are so few experts at this meeting. Feel free to respond to this email with your thoughts on the last time an adcomm had fewer than 10 voting members.

.
Zachary Brennan
Senior Editor, Endpoints News
@ZacharyBrennan
1
by Zachary Brennan

The FDA said Wednes­day that the con­fir­ma­to­ry tri­al that Ei­sai and Bio­gen ran to show their new Alzheimer's drug has a clin­i­cal ben­e­fit did in­deed have one, lin­ing Leqem­bi up for a like­ly full ap­proval next month af­ter get­ting an ac­cel­er­at­ed nod in Jan­u­ary.

Ahead of Fri­day's ad­vi­so­ry com­mit­tee meet­ing, FDA re­view­ers af­firmed what Ei­sai and Bio­gen said at the time about the re­sults of the con­fir­ma­to­ry tri­al, known as CLAR­I­TY AD, adding that:

Any group-lev­el mean change from base­line on the CDR-SB that is re­duced, to a sta­tis­ti­cal­ly sig­nif­i­cant ex­tent in an ap­pro­pri­ate­ly pow­ered study, com­pared to place­bo is con­sid­ered clin­i­cal­ly mean­ing­ful.

The agency al­so said that the pos­i­tive find­ing on the pri­ma­ry end­point is sup­port­ed by sta­tis­ti­cal­ly sig­nif­i­cant re­sults for all four mul­ti­plic­i­ty-con­trolled sec­ondary end­points, "in­clud­ing clin­i­cal end­points cap­tur­ing dis­tinct in­for­ma­tion re­gard­ing cog­ni­tive de­cline."

As far as safe­ty-re­lat­ed is­sues, which in­clude amy­loid-re­lat­ed imag­ing ab­nor­mal­i­ties (ARIA), cere­bral he­m­or­rhage, and in­fu­sion-re­lat­ed re­ac­tions and hy­per­sen­si­tiv­i­ty, the FDA re­view­ers sound­ed pos­i­tive again, say­ing the "risks do not ap­pear to pre­clude tra­di­tion­al ap­proval. Risk can be mit­i­gat­ed through a de­scrip­tion in la­bel­ing and rec­om­men­da­tions for mon­i­tor­ing and dose man­age­ment guide­lines as pro­vid­ed for in la­bel­ing."

A pos­i­tive vote will like­ly mean a swift full ap­proval and wider cov­er­age from both the CMS and pri­vate in­sur­ers, which un­til now have lim­it­ed the use of Leqem­bi and Bio­gen's Aduhelm to clin­i­cal tri­als de­spite their ac­cel­er­at­ed ap­provals. CMS re­cent­ly said it plans to cov­er Leqem­bi if it re­ceives full ap­proval. The drug's PDU­FA date is Ju­ly 6.

Click here to continue reading
2
by Zachary Brennan

The FDA's ad­vi­so­ry com­mit­tees of out­side ex­perts are sup­posed to of­fer the agency with un­bi­ased re­views of the spon­sor's ef­fi­ca­cy and safe­ty da­ta be­fore them. And while oc­ca­sion­al­ly the FDA will al­low cer­tain tan­gen­tial­ly paid con­sul­tants (e.g. from a com­pet­ing firm), those re­la­tion­ships must be dis­closed ahead of time, and waivers from that COI need to be grant­ed.

In the case of David Weis­man, a neu­rol­o­gist with Penn­syl­va­nia-based Abing­ton Neu­ro­log­i­cal As­so­ciates who worked on clin­i­cal tri­als for Ei­sai and Bio­gen, the FDA had sought his ex­per­tise in Fri­day's ad­comm that will dis­cuss whether to con­vert Ei­sai's new Alzheimer's drug Leqem­bi (lecanemab) in­to a full ap­proval. The de­ci­sion is like­ly to be one in fa­vor of Leqem­bi, open­ing the door for wider sales na­tion­wide with CMS cov­er­age.

The on­ly is­sue with Weis­man­'s par­tic­i­pa­tion in the meet­ing, as ex­plained in his waiv­er to par­tic­i­pate, is that he's re­ceived tens of thou­sands of dol­lars from Ei­sai and part­ner Bio­gen over the last five years, and been vo­cal about his sup­port for lecanemab, mak­ing his im­par­tial­i­ty a ques­tion mark.

And while the FDA praised how he is "high­ly re­spect­ed in­ter­na­tion­al­ly for his deep in­sights and broad per­spec­tives, and he has been high­ly val­ued as a mem­ber of the Pe­riph­er­al and Cen­tral Ner­vous Sys­tem Drugs Ad­vi­so­ry Com­mit­tee" as re­cent­ly as March to dis­cuss Bio­gen's tofersen, a treat­ment of ALS ap­proved in April, oth­ers won­dered if there were not bet­ter op­tions.

Weis­man an­nounced on Twit­ter to­day that he would not par­tic­i­pate in the pan­el.

Click here to continue reading
Chiquita Brooks-LaSure, Centers for Medicare and Medicaid Services administrator (AP Photo/Evan Vucci)
3
by Zachary Brennan

As Con­gres­sion­al and ad­vo­ca­cy group pres­sure has been heat­ed, the Cen­ters for Medicare and Med­ic­aid Ser­vices reaf­firmed to­day that if amy­loid-tar­get­ed drugs to slow the pro­gres­sion of Alzheimer’s dis­ease win full ap­proval — not just ac­cel­er­at­ed ap­proval — then Medicare will cov­er treat­ment where re­al-world da­ta can be col­lect­ed.

The of­fi­cial cov­er­age-is-com­ing an­nounce­ment, which had been pre­vi­ous­ly men­tioned by Ei­sai, Bio­gen and CMS of­fi­cials sep­a­rate­ly, ar­rives as Ei­sai and Bio­gen's Leqem­bi (lecanemab) faces an ad­vi­so­ry com­mit­tee meet­ing of out­side FDA ex­perts next Fri­day.

That same FDA ad­comm pre­vi­ous­ly vot­ed unan­i­mous­ly against the ap­proval of Bio­gen's oth­er amy­loid-tar­get­ed drug Aduhelm (ad­u­canum­ab), which still went on to win an ac­cel­er­at­ed ap­proval in 2021. Three mem­bers of the com­mit­tee, in­clud­ing Wash­ing­ton Uni­ver­si­ty in St. Louis' Joel Perl­mut­ter, Har­vard's Aaron Kessel­heim and the Mayo Clin­ic's David Knop­man re­signed af­ter the FDA made its ac­cel­er­at­ed ap­proval de­ci­sion.

But Aduhelm still faced CM­S' neg­a­tive cov­er­age de­ter­mi­na­tion — which so far has ap­plied to all amy­loid-tar­get­ed drugs un­der ac­cel­er­at­ed ap­proval — that there would be no cov­er­age out­side of clin­i­cal tri­als. Aduhelm has gone on to muster min­i­mal sales.

But Leqem­bi may be dif­fer­ent. Af­ter re­ceiv­ing ac­cel­er­at­ed ap­proval in Jan­u­ary, the drug will like­ly be the first to win full ap­proval on or be­fore Ju­ly 6, de­pend­ing on the re­sults of next week's ad­comm.

"If the FDA grants tra­di­tion­al ap­proval CMS is pre­pared to en­sure any­one with Medicare Part B who meets the cri­te­ria is cov­ered," CMS chief Chiq­ui­ta Brooks-La­Sure said in a state­ment.

Click here to continue reading
FDA Commissioner Robert Califf (Tom Williams/CQ Roll Call via AP Images)
4
by Nicole DeFeudis

FDA Com­mis­sion­er Rob Califf told BIO CEO Rachel King on Wednes­day that it’s “im­pos­si­ble to ar­gue that the US is do­ing well in health,” high­light­ing high drug prices and mis­in­for­ma­tion as two key chal­lenges.

The com­mis­sion­er al­so took the op­por­tu­ni­ty to dis­cuss ac­cel­er­at­ed ap­proval re­forms, at­tri­tion at the agency and the In­fla­tion Re­duc­tion Act, which came in­to fo­cus ear­li­er this week when Mer­ck filed a law­suit call­ing parts of the drug pric­ing law a sham. In­dus­try crit­ics have ar­gued that the leg­is­la­tion will have a chill­ing ef­fect on in­no­va­tion.

When asked about the IRA, Califf re­spond­ed that “the prices of drugs are too high.”

“We have to come up with a bet­ter sys­tem. And the IRA is an ef­fort to do that,” he said, lat­er adding that “all of these big laws have im­per­fec­tions,” but he’s “not at lib­er­ty to talk about spe­cif­ic de­tails of what I think is im­per­fect.”

He dis­cussed ramp­ing up com­mu­ni­ca­tions with CMS, not just as part of the IRA, but “on mul­ti­ple fronts.”

“There’s some­thing miss­ing in the equa­tion by which we trans­late all this amaz­ing in­no­va­tion in­to prod­ucts and ser­vices that help the pop­u­la­tion,” he said.

CMS said ear­li­er this year that it in­tends to work close­ly with the FDA on ac­cel­er­at­ed ap­proval pay­ment re­forms in a pi­lot pro­gram de­signed to “re­duce Medicare spend­ing on drugs that have no con­firmed clin­i­cal ben­e­fit.”

Click here to continue reading
5
by Andrew Dunn

Mer­ck has filed a law­suit in fed­er­al court to try and in­val­i­date the In­fla­tion Re­duc­tion Act, tak­ing the lead in the phar­ma in­dus­try's op­po­si­tion to the land­mark drug pric­ing law.

The 28-page suit against the US De­part­ment of Health and Hu­man Ser­vices pulls few punch­es in its rhetoric, crit­i­ciz­ing parts of the law as a sham and clos­er to ex­tor­tion than ne­go­ti­a­tion. The heart of Mer­ck’s le­gal ar­gu­ment, filed Tues­day morn­ing in the US Dis­trict Court for the Dis­trict of Co­lum­bia, claims the bill vi­o­lates the First and Fifth Amend­ments.

"By co­erc­ing Mer­ck to pro­vide its drug prod­ucts at gov­ern­ment-set prices, the pro­gram takes prop­er­ty for pub­lic use with­out just com­pen­sa­tion," Mer­ck said in a state­ment ac­com­pa­ny­ing the suit. "Mer­ck in­tends to lit­i­gate this mat­ter all the way to the US Supreme Court if nec­es­sary."

The IRA was signed in­to law last Au­gust, giv­ing Medicare the pow­er to ne­go­ti­ate prices for a lim­it­ed num­ber of drugs. The law was a win for Pres­i­dent Joe Biden and De­moc­rats, who have at­tempt­ed to bring for­ward a drug price law for years, and a rare de­feat for phar­ma on Capi­tol Hill.

The HHS is set to se­lect the first 10 drugs in Sep­tem­ber — and Mer­ck said in the law­suit that it ex­pects its di­a­betes block­buster Janu­via, which sold $4.5 bil­lion last year, will be on the list.

A drug­mak­er law­suit is far from un­ex­pect­ed — the on­ly ques­tion has been which com­pa­ny would ac­tu­al­ly move against the law. In­dus­try ex­ec­u­tives and trade groups have de­cried the bill even be­fore it be­came law, say­ing it’s clos­er to price-set­ting than ne­go­ti­a­tions, and hint­ed that le­gal chal­lenges were be­ing con­sid­ered.

Click here to continue reading
Rob Davis, Merck CEO (The Galien Foundation)
6
by Jaimy Lee, Nicole DeFeudis, Andrew Dunn

Mer­ck may be the first com­pa­ny to sue and try to stop the In­fla­tion Re­duc­tion Act. But it al­most cer­tain­ly won’t be the on­ly one.

The law­suit like­ly aims to stop the US from pub­lish­ing the first list of drugs that would be sub­ject to pric­ing ne­go­ti­a­tion by Medicare, with Mer­ck al­leg­ing that the IRA vi­o­lates the First and Fifth Amend­ments by forc­ing the com­pa­ny to give dis­counts with­out the op­tion of walk­ing away, ac­cord­ing to the suit, which was filed Tues­day in the US Dis­trict Court for the Dis­trict of Co­lum­bia.

Mer­ck, which is large­ly viewed as a staid cor­po­rate leader, de­scribed the leg­is­la­tion as “po­lit­i­cal Kabu­ki the­ater” in the law­suit. How­ev­er, HHS said it plans to de­fend the drug price ne­go­ti­a­tion law. “The law is on our side,” HHS Sec­re­tary Xavier Be­cer­ra said in a state­ment.

Mer­ck is al­most cer­tain to have al­lies quick­ly join its side. Just hours af­ter the law­suit was filed, Bio­gen CEO Chris Viehbach­er said at the BIO meet­ing in Boston that he was­n't sur­prised by the suit and agreed with its de­scrip­tion of the IRA as “ex­tor­tion." Viehbach­er, the for­mer CEO of French phar­ma Sanofi, said the law goes far be­yond the rules in less phar­ma-friend­ly Eu­rope.

"The gov­ern­ments in Eu­rope nev­er put any­thing any­where near the dra­con­ian mea­sures that are in the IRA," he said.

Viehbach­er said he would­n't be sur­prised if more com­pa­nies file law­suits, and that Bio­gen is look­ing at that op­tion. PhRMA, the in­dus­try lob­by­ing group, al­so ap­peared to raise the specter of ad­di­tion­al law­suits.

Click here to continue reading
7
by Tyler Patchen

The FDA is hop­ing its lat­est so­lu­tion will stave off the con­tin­ued short­age of cis­platin, a key drug used in treat­ing sev­er­al types of can­cer.

Be­gin­ning to­mor­row, or­ders can be placed for cis­platin ship­ments from Chi­na-based Qilu Phar­ma­ceu­ti­cal Co., which worked in co­or­di­na­tion with the FDA and gener­ic drug­mak­er Apo­tex to try to help with the short­age.

FDA Com­mis­sion­er Robert Califf said on Fri­day that the agency be­gan the process to im­port cer­tain “for­eign-ap­proved ver­sions” of cis­platin from FDA-reg­is­tered fa­cil­i­ties. Ac­cord­ing to a doc­u­ment, Qilu has start­ed the “tem­po­rary im­por­ta­tion” of cis­platin in­to the US even though the in­jec­tion from Qilu is mar­ket­ed and man­u­fac­tured in Chi­na and is not ap­proved by the FDA.

But Califf was adamant in his post that in sit­u­a­tions re­quir­ing im­por­ta­tion, the agency will “care­ful­ly as­sess prod­uct qual­i­ty” and re­quire the man­u­fac­tur­ers to en­sure the prod­ucts are safe.

https://twit­ter.com/Dr­Califf

How­ev­er, no de­tails as to the phys­i­cal amounts or what steps Qilu is tak­ing to com­ply with the FDA were im­me­di­ate­ly avail­able. End­points News did reach out to Qilu but did not re­ceive a re­sponse by press time.

The cis­platin short­age has been weigh­ing on the FDA. Last week, Richard Paz­dur, di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, told The Can­cer Let­ter that to re­store the cis­platin sup­ply the FDA is of­fer­ing as­sis­tance to man­u­fac­tur­ers to boost pro­duc­tion and look at the tem­po­rary im­por­ta­tion.

The im­por­ta­tion of the drug is be­ing met as a pos­i­tive step by ex­perts, but fur­ther steps do need to be tak­en to re­solve the sit­u­a­tion.

Click here to continue reading
Sen. Ron Wyden (D-OR) (Francis Chung/E News/POLITICO via AP Images)
8
by Tyler Patchen

Sen. Ron Wyden (D-OR) is putting pres­sure on reg­u­la­tors to ad­dress an on­go­ing short­age of am­phet­a­mine mixed salts, a gener­ic form of Adder­all that treats AD­HD.

The sen­a­tor said in let­ters last week to DEA Ad­min­is­tra­tor Anne Mil­gram and FDA Com­mis­sion­er Robert Califf that he is "deeply dis­ap­point­ed on be­half of the Ore­go­ni­ans I rep­re­sent" over the agen­cies' re­sponse to the short­age.

“While I ap­pre­ci­ate that your staff fol­lowed up with more in­for­ma­tion on the role the Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) plays in pre­vent­ing and mit­i­gat­ing drug short­ages, it falls short of the state­ment and ac­tions need­ed. Specif­i­cal­ly, the process is mud­dy and ob­scure as to how gener­ic man­u­fac­tur­ers are nav­i­gat­ing the process to re­quest a quo­ta in­crease, and the fact that your agency does not seek out or re­port re­gion­al da­ta is a grave con­cern,” the let­ter said.

Wyden added that he con­tin­ues to sup­port ac­tion that would es­tab­lish re­quire­ments for man­u­fac­tur­ers to re­port sus­tained in­creas­es in de­mand, but un­til that ac­tion is tak­en, he be­lieves "the agency has a re­spon­si­bil­i­ty to pro­vide clear guid­ance and out­reach to man­u­fac­tur­ers of these es­sen­tial med­ica­tions that are now dif­fi­cult to ac­cess."

“The agency should re­quest up­dates from man­u­fac­tur­ers on their abil­i­ty to meet con­sumer de­mand, and in­form the pub­lic ac­cord­ing­ly,” the let­ter said. "You have au­thor­i­ty and op­por­tu­ni­ty to move us to­ward so­lu­tions to these sig­nif­i­cant drug short­ages.”

Click here to continue reading
9
by Tyler Patchen

Foghorn Ther­a­peu­tics, a gene-fo­cused biotech, has been giv­en the all-clear to pro­ceed with a tri­al as­sess­ing its ther­a­py aimed at treat­ing can­cers found in the blood and bone mar­row.

Foghorn said Mon­day that the FDA lift­ed the clin­i­cal hold on its Phase I monother­a­py dose es­ca­la­tion study of FHD-286 to treat acute myel­oge­nous leukemia (AML) and myelodys­plas­tic syn­drome (MDS).

Last Au­gust, the com­pa­ny at­trib­uted the FDA's clin­i­cal hold to sus­pect­ed cas­es of fa­tal dif­fer­en­ti­a­tion syn­drome, which was be­lieved to be re­lat­ed to FHD-286. Dif­fer­en­ti­a­tion syn­drome is a side ef­fect that is as­so­ci­at­ed with treat­ments for AML and MDS; it can cause trou­ble breath­ing, low blood pres­sure, and kid­ney fail­ure and it can be life-threat­en­ing, as well, if it's not treat­ed.

How­ev­er, the FDA lift­ed the hold last week af­ter Foghorn changed some of the pro­to­cols in the tri­al. The com­pa­ny now plans to start a Phase I study of FHD-286 in com­bi­na­tion with the chemother­a­pies decitabine or low-dose cy­tara­bine (LDAC) in AML pa­tients who have re­lapsed in the third quar­ter of this year.

“Clin­i­cal da­ta sug­gest FHD-286 is a po­tent, broad-based dif­fer­en­ti­a­tion ther­a­peu­tic, and we be­lieve it has sig­nif­i­cant com­bi­na­tion po­ten­tial as a treat­ment in AML,” Foghorn CEO Adri­an Gottschalk said in a re­lease.

Foghorn's stock price FHTX was up about 11% on Mon­day morn­ing.

Click here to continue reading
10
by Lei Lei Wu

The FDA has lift­ed a par­tial clin­i­cal hold on Mol­e­c­u­lar Tem­plates’ ear­ly-stage tri­al for a mul­ti­ple myelo­ma drug, the biotech com­pa­ny an­nounced Thurs­day morn­ing.

Reg­u­la­tors had put the tri­al on par­tial hold in ear­ly April, paus­ing pa­tient en­roll­ment, fol­low­ing two ad­verse heart-re­lat­ed events in pa­tients who re­ceived the high­est dose of Mol­e­c­u­lar Tem­plates’ treat­ment MT-0169 last year. One pa­tient had asymp­to­matic grade 2 my­ocardi­tis, or heart mus­cle in­flam­ma­tion, while the oth­er had a grade 3 car­diomy­opa­thy. Both re­cov­ered with­in two months.

Mol­e­c­u­lar Tem­plates’ mul­ti­ple myelo­ma drug is an en­gi­neered tox­in body, which fea­tures a tar­get­ing an­ti­body do­main fused to an en­gi­neered bac­te­r­i­al pro­tein that in­duces cell death. The drug tar­gets CD38, which is high­ly ex­pressed in mul­ti­ple myelo­ma cells, in hopes of killing those cells.

The Austin, TX-based biotech said it's fo­cus­ing on study­ing the drug can­di­date in ex­tramedullary myelo­ma, an ag­gres­sive form of the dis­ease in which tu­mors form out­side the bone mar­row.

Just be­fore the clin­i­cal hold, Mol­e­c­u­lar Tem­plates laid off more than 100 work­ers — ap­prox­i­mate­ly half its staff — and cut back on re­search work to fo­cus on three clin­i­cal pro­grams in­clud­ing the mul­ti­ple myelo­ma one.

John Carroll
Editor & Founder
Arsalan Arif
Publisher & Founder
Igor Yavych
Chief Technical Officer
Valentin Manov
Creative Director
Drew Armstrong
Executive Editor
Amanda Florez
Chief of Staff
Amber Tong
Senior Editor
Max Gelman
Senior Editor
Zachary Brennan
Senior Editor
Beth Snyder Bulik
Senior Editor
Melissa Nazzaro
Sales Director
Julie Notario
Sales Director
Kari Abitbol
Director, Client Success
James Cherrick
Controller
Ryan McRae
Chief Revenue Officer
and many more
Endpoints News
2029 Becker Drive; Lawrence, Kansas 66047 USA Privacy and deletion: help@endpointsnews.com
web twitter linkedin
Worldwide made. Thanks for reading.
FT Specialist Logo A service from the Financial Times