House De­moc­rats are on the cusp of pass­ing two ma­jor pieces of Biden's agen­da Fri­day, but Medicare drug price ne­go­ti­a­tions — once the cen­ter­piece of the Build Back Bet­ter Ac­t's rev­enue stream — has been rel­e­gat­ed to on­ly about $100 bil­lion in sav­ings over the next decade. That num­ber fell low­er yes­ter­day.

Over­all, the com­pro­mise end­ed up win­ning over both De­mo­c­rat sen­a­tors re­ceiv­ing PhRMA cash, like Kyrsten Sine­ma and Bob Menen­dez, and more lib­er­al sen­a­tors, like Eliz­a­beth War­ren. But on the House side, the bat­tle con­tin­ued up un­til yes­ter­day evening.

PhRMA al­ly Rep. Scott Pe­ters (D-CA) wran­gled an­oth­er year of ex­clu­siv­i­ty for bi­o­log­ics be­fore Medicare will be able to ne­go­ti­ate prices, mean­ing ne­go­ti­a­tions will now be­gin af­ter 13 years (in­stead of 12 in the orig­i­nal text). Pe­ter­s' of­fice did not con­firm the change, but a source work­ing on the ne­go­ti­a­tions con­firmed that it's 13 years now for bi­o­log­ics.

While one year may seem slight, the move could sub­tract bil­lions in sav­ings from the deal. And such a shift would like­ly be mu­sic to the ears of Mer­ck and Bris­tol My­ers Squibb.

Mer­ck­'s Keytru­da and Bris­tol My­ers Squibb’s Op­di­vo, both check­point in­hibitors and two of the biggest block­buster bi­o­log­ic can­cer drugs in the world, would now each get an ex­tra year of ne­go­ti­a­tion-free sales. Medicare Part B spent more than $4 bil­lion on the drugs com­bined in 2019, which un­der the new deal would­n't see ne­go­ti­a­tions from Medicare un­til 2027, as they were first FDA ap­proved in 2014.

Al­though House and Sen­ate De­moc­rats have fi­nal­ly cracked their Mis­sion: Im­pos­si­ble to al­low the fed­er­al gov­ern­ment to ne­go­ti­ate some drug prices, the ne­go­ti­a­tions will in­clude so few drugs and have so many stip­u­la­tions at­tached that the end re­sult may be more of a drop in the ocean than the mon­soon that drug price ne­go­ti­a­tions could've been.

Con­gress is wait­ing for a CBO score be­fore of­fi­cial­ly vot­ing, but ear­ly es­ti­mates point to about $100 bil­lion in drug pric­ing sav­ings over ten years from the deal. That's ba­si­cal­ly the equiv­a­lent of what the phar­ma in­dus­try spends on DTC mar­ket­ing over a decade. Or about five years of what phar­ma com­pa­nies spend on mar­ket­ing to health care pro­fes­sion­als.

The Medicare ne­go­ti­a­tions deal is al­so com­pli­cat­ed by ex­ten­sive lim­i­ta­tions — it's on­ly for ex­pen­sive Medicare Part D and B drugs, 10 to start, the drugs must have no gener­ic/biosim­i­lar com­peti­tors, and the ne­go­ti­a­tions can on­ly start post-ex­clu­siv­i­ty, or 9 years af­ter the launch of small mol­e­cule drugs and 13 years for bi­o­log­ics. It's un­clear what kind of dent, if any, the deal will make on drug prices over the longer term, or for those out­side of Medicare.

"CMS will de­ter­mine the fi­nal price, based on cri­te­ria that are rather pro-in­dus­try – thus it seems more of a no­tice-and-com­ment rather than ac­tu­al ne­go­ti­a­tion," Bern­stein biotech an­a­lyst Ron­ny Gal wrote in a re­cent in­vestor note. "Our ear­ly im­pres­sion is that the net im­pact is pos­i­tive for phar­ma stocks."

McK­in­sey is un­der fire again, this time from the House Over­sight Com­mit­tee, which is dig­ging in­to the con­sult­ing fir­m's close ties to the FDA while work­ing si­mul­ta­ne­ous­ly to pro­mote opi­oids and find ways to stall com­pe­ti­tion for Ab­b­Vie's block­buster rheuma­toid arthri­tis drug Hu­mi­ra.

Since 2008, FDA has paid McK­in­sey over $140 mil­lion for var­i­ous tasks re­lat­ing to opi­oids, drug safe­ty, and drug ap­provals, as well as a “track and trace” sys­tem for drugs, mon­i­tor­ing pro­grams to as­sess drug safe­ty, and ways to stream­line the drug ap­proval process.

But Pur­due Phar­ma’s records show, ac­cord­ing to the com­mit­tee, that at the same time McK­in­sey was ad­vis­ing FDA, in­clud­ing of­fices re­spon­si­ble for opi­oid pro­grams, the com­pa­ny was al­so ad­vis­ing Pur­due on how to lob­by the FDA.

"For in­stance, in 2008, FDA pro­posed new safe­ty rules for Oxy­Con­tin un­der the agency’s Risk Eval­u­a­tion and Mit­i­ga­tion Strate­gies (REMS) pro­gram—in­clud­ing a re­quire­ment that the painkiller could be pre­scribed on­ly by spe­cial­ly trained phar­ma­cies or health­care prac­ti­tion­ers," the com­mit­tee says. Pur­due hired McK­in­sey, which suc­cess­ful­ly re­buffed stronger REMS safe­ty mea­sures un­til 2012, de­spite the ob­jec­tions of an in­de­pen­dent pan­el of ex­perts who rec­om­mend­ed more rig­or­ous train­ing for pre­scribers and the re­duc­tion of in­dus­try in­flu­ence in the safe­ty mea­sures.

"It is not known to what ex­tent McK­in­sey con­sult­ed for the opi­oid in­dus­try dur­ing this same pe­ri­od, how much McK­in­sey re­ceived in com­pen­sa­tion from opi­oid-re­lat­ed en­ti­ties, or whether FDA con­sult­ed with McK­in­sey on the de­ci­sion to re­ject stronger safe­ty rules," the com­mit­tee's let­ter to McK­in­sey on Fri­day said.

Back in March 2019, the FDA made clear to Sanofi and its part­ner Lex­i­con Phar­ma­ceu­ti­cals that it could­n't ap­prove the ap­pli­ca­tion for their di­a­betes drug be­cause the da­ta sub­mit­ted do not show that the drug is safe.

"The da­ta demon­strat­ed that the ad­di­tion of so­tagliflozin to in­sulin is as­so­ci­at­ed with an in­creased risk of di­a­bet­ic ke­toaci­do­sis (DKA), a se­ri­ous and of­ten life-threat­en­ing con­se­quence of in­sulin in­suf­fi­cien­cy," the agency said in a rare ex­pla­na­tion of the com­plete re­sponse let­ter. "Time-to-event analy­ses of the clin­i­cal tri­al da­ta showed ear­li­er de­vel­op­ment of DKA in so­tagliflozin-treat­ed pa­tients than in pa­tients as­signed to place­bo, with­out ev­i­dence that the risk stopped in­creas­ing over time."

While FDA said the clin­i­cal tri­al da­ta showed that so­tagliflozin, which is ap­proved in the EU, re­duced HbA1c, a val­i­dat­ed sur­ro­gate end­point due to im­proved glycemic con­trol, the agency al­so said the ef­fect "was mod­est." The FDA’s En­docrino­log­ic and Meta­bol­ic Drugs Ad­vi­so­ry Com­mit­tee split 8-8 on whether the over­all ben­e­fits out­weighed the risks.

"Di­a­bet­ic ke­toaci­do­sis is an in­her­ent risk of type 1 di­a­betes and an in­crease was seen with so­tagliflozin com­pared to in­sulin alone," Lex­i­con CMO Pablo La­puer­ta said in a state­ment af­ter the ad­comm vote. "We be­lieve this can po­ten­tial­ly be ad­dressed with prop­er ed­u­ca­tion and mon­i­tor­ing.”

Typ­i­cal­ly, com­pa­nies that re­ceive CRLs try to work with FDA, ad­dress the de­fi­cien­cies out­lined, and re­sub­mit their ap­pli­ca­tion as quick­ly as pos­si­ble for ap­proval.

Wash­ing­ton DC's dis­trict court hand­ed No­var­tis a clear win late Fri­day, ar­gu­ing that the Big Phar­ma can place con­di­tions on the sales of drugs dis­count­ed by a fed­er­al pro­gram to con­tract phar­ma­cies. But this in­ter­pre­ta­tion was con­tra­dict­ed by an­oth­er de­ci­sion hand­ed down Fri­day in a New Jer­sey dis­trict court, in which No­vo Nordisk and Sanofi were told that they can­not uni­lat­er­al­ly im­pose re­stric­tions on the 340B pro­gram and that their new poli­cies "must cease."

The con­flict­ing opin­ions are just the lat­est in a le­gal bat­tle sweep­ing the coun­try be­tween the Biden ad­min­is­tra­tion's HRSA, cre­at­ing a piece­meal of in­ter­pre­ta­tions of the pro­gram and how to en­force it. HRSA has strug­gled to reg­u­late the drug dis­count pro­gram for the need­i­est Amer­i­cans, both in terms of deal­ing with the phar­ma com­pa­nies, who are chal­leng­ing what they see as a bal­loon­ing pro­gram (to al­most 10% of the en­tire US phar­ma mar­ket), and the pro­lif­er­a­tion of con­tract phar­ma­cies re­ceiv­ing these steep dis­counts.

DC Judge Dab­ney Friedrich made clear in her opin­ion that drug­mak­ers are right to chal­lenge re­cent­ly levied fines from HRSA due to the com­pa­nies' new­ly en­act­ed re­stric­tions around these con­tract phar­ma­cies, writ­ing, "The statute's plain lan­guage, pur­pose, and struc­ture do not pro­hib­it drug man­u­fac­tur­ers from at­tach­ing any con­di­tions to the sales of cov­ered drugs through con­tract phar­ma­cies."

One of the ma­jor rea­sons the FDA's ac­cel­er­at­ed ap­proval path­way re­ceives so many ac­co­lades and so much sup­port is that it speeds new and hope­ful­ly im­proved drugs to pa­tients, usu­al­ly in on­col­o­gy, while con­fir­ma­to­ry ev­i­dence on the clin­i­cal ben­e­fit can be gath­ered.

But a new re­search let­ter pub­lished Tues­day in JA­MA Net­work Open rais­es fresh ques­tions about the path­way, mak­ing the case that be­cause the dif­fer­ence in the amount of time it takes to run the con­fir­ma­to­ry tri­al vs. the piv­otal tri­al is typ­i­cal­ly sim­i­lar, the com­pa­nies might as well run the equiv­a­lent of the con­fir­ma­to­ry tri­al first.

The re­search comes as HHS is look­ing in­to the ac­cel­er­at­ed path­way, and as FDA has been sharply crit­i­cized for us­ing the path­way to ap­prove Bio­gen's Alzheimer's drug, de­spite scant ev­i­dence that it ac­tu­al­ly pro­vides a clin­i­cal ben­e­fit. The FDA al­so grant­ed Bio­gen a long run­way (9 years) to com­plete its con­fir­ma­to­ry tri­al.

Look­ing at 32/45 in­di­ca­tions ap­proved via the ac­cel­er­at­ed path­way, the Yale re­searchers, led by first au­thor Joshua Wal­lach, found that over­all the me­di­an piv­otal tri­al du­ra­tion was 10 months, while the post-ap­proval tri­al du­ra­tion was 17 months.

"These find­ings raise ques­tions about the use of ac­cel­er­at­ed ap­proval pro­gram for cer­tain ther­a­peu­tic agents, es­pe­cial­ly if postap­proval con­fir­ma­to­ry tri­als nei­ther con­sis­tent­ly eval­u­ate clin­i­cal out­comes nor are much longer than piv­otal tri­als us­ing sur­ro­gate end­points," the au­thors not­ed.

They al­so cit­ed the in­cred­i­bly long de­lay be­tween the time of the ac­cel­er­at­ed nod and when the con­fir­ma­to­ry tri­al re­sults are ac­tu­al­ly re­port­ed.

Mod­er­na’s on­go­ing feud with the NIH over Covid-19 vac­cine patents has spilled in­to the open.

In a new re­port from the New York Times pub­lished Tues­day af­ter­noon, Mod­er­na is as­sert­ing that three NIH sci­en­tists were not in­volved in in­vent­ing the key com­po­nent in the biotech’s vac­cine, to the sur­prise of the in­sti­tute. The claim comes from a Ju­ly fil­ing with the US Patent and Trade­mark Of­fice, which the NYT post­ed in full along with its re­port.

With­in the fil­ing, Mod­er­na said it had “reached the good-faith de­ter­mi­na­tion” that three NIH sci­en­tists — John Mas­co­la, Bar­ney Gra­ham and Kizzmekia Cor­bett — “did not co-in­vent” the se­quence that prompts the body’s im­mune re­sponse to the coro­n­avirus spike pro­tein. The NIH, mean­while, says the trio worked with Mod­er­na at the out­set of the pan­dem­ic to de­sign the com­po­nent in ques­tion.

In re­sponse to an End­points News re­quest for com­ment, a Mod­er­na spokesper­son said the com­pa­ny has "all along" rec­og­nized the role the NIH played in de­vel­op­ing the Covid-19 shot. But the spokesper­son in­sist­ed on­ly Mod­er­na sci­en­tists in­vent­ed mR­NA-1273 — the co­de­name for the com­pa­ny's vac­cine.

The spokesper­son al­so claimed that Mod­er­na was­n't not al­lowed to "choose" who to list on the patent ap­pli­ca­tion, per US law. It's not clear to which law or laws Mod­er­na is re­fer­ring to.

"Fol­low­ing those rules, as we must, Mod­er­na is re­quired to on­ly list Mod­er­na sci­en­tists as the in­ven­tors for the patent claims to mR­NA-1273," the spokesper­son wrote in an email. "Mod­er­na’s con­clu­sion is dri­ven by noth­ing oth­er than our oblig­a­tion to com­ply with U.S. patent law."

The FDA’s Psy­chophar­ma­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee on Thurs­day vot­ed 12 to 1 against ap­prov­ing Le­vo Ther­a­peu­tics’ nasal spray for Prad­er-Willi syn­drome, a dif­fi­cult-to-treat dis­ease that leaves pa­tients with con­stant, in­sa­tiable hunger.

Those who vot­ed no raised con­cerns about a lack of sub­stan­tial ev­i­dence, as a 9.6 mg dose of the drug failed the pri­ma­ry end­points in a Phase III tri­al. Look­ing for a sil­ver lin­ing, Le­vo turned to a 3.2 mg dose which met the tri­al’s sec­ondary end­points. But ad­comm mem­bers won­dered whether Le­vo could repli­cate those pos­i­tive re­sults.

“The thing that stuck out to me most was that the 9.6 dose study did not repli­cate,” com­mit­tee mem­ber Satish Iyen­gar, chair of the Uni­ver­si­ty of Pitts­burgh’s sta­tis­tics de­part­ment, said af­ter the vote. “And giv­en the fact that the 3.2 dose study did­n't re­al­ly hold up strong­ly to the sen­si­tiv­i­ty analy­sis that they did, I just have no con­fi­dence — I have lit­tle con­fi­dence — that it will repli­cate.”

An­oth­er pan­el mem­ber, UCLA psy­chi­a­try pro­fes­sor Wal­ter Dunn, sug­gest­ed that if the ques­tion had asked about “mod­er­ate ev­i­dence of ef­fec­tive­ness,” he would have re­con­sid­ered his vote.

“I do think it's in­ter­est­ing that this is word­ed this way, be­cause it does­n't talk at all about any pos­si­ble risk-ben­e­fit trade-off,” said James Troen­dle, a math­e­mat­i­cal sta­tis­ti­cian at the NIH.

Le­vo’s can­di­date, dubbed LV-101, is an in­tranasal form of car­be­tocin, a drug used out­side the US to con­trol bleed­ing af­ter child­birth. It’s an oxy­tocin re­cep­tor ag­o­nist that was orig­i­nal­ly be­ing de­vel­oped for PWS by Fer­ring Phar­ma­ceu­ti­cals, un­til Le­vo snagged the rights in 2016. Oxy­tocin is a neu­ro­trans­mit­ter that reg­u­lates so­cial-emo­tion­al and feed­ing be­hav­iors, and re­search shows that those with PWS don’t have enough of it.

Af­ter a fi­as­co sur­round­ing the con­t­a­m­i­na­tion of Covid-19 vac­cine dos­es in its fa­cil­i­ties — dur­ing a time in which vac­ci­nat­ing res­i­dents was dire to Amer­i­ca's re­turn to nor­mal­cy — Emer­gent BioSo­lu­tion­s' $600 mil­lion man­u­fac­tur­ing deal with the US gov­ern­ment has come to an end.

CEO Bob Kramer said that the two par­ties "mu­tu­al­ly agreed" to ter­mi­nate the con­tract in an earn­ings call with in­vestors Thurs­day, evap­o­rat­ing about $180 mil­lion in deal val­ue.

The com­pa­ny will con­tin­ue pro­duc­ing J&J's Covid-19 vac­cine un­der a sep­a­rate deal.

Emer­gent had first land­ed a deal with BAR­DA to set up a pub­lic-pri­vate part­ner­ship for pan­dem­ic pre­pared­ness back in 2012, award­ing $163 mil­lion to ex­pand its Bal­ti­more site. Last May, through Op­er­a­tion Warp Speed, the feds beefed up the ex­ist­ing re­la­tion­ship to re­serve ca­pac­i­ty and scale up the op­er­a­tions, in hopes of se­cur­ing a re­li­able do­mes­tic man­u­fac­tur­er of ade­n­ovirus-based vac­cines be­ing de­vel­oped by J&J (now au­tho­rized) and As­traZeneca (yet to be au­tho­rized).

While Kramer said the ex­e­cu­tion of the pan­dem­ic pre­pare­ness ini­tia­tive and the nec­es­sary op­er­a­tional in­vest­ments "by all ad­min­is­tra­tions" fell short, he stuck to his guns, stat­ing that when the pan­dem­ic first be­gan, Emer­gent was just one of two orig­i­nal part­ners re­main­ing in the pro­gram, echo­ing past sen­ti­ments that the CD­MO de­served a pat on the back for be­ing ready to take on the task — and the mas­sive amount of mon­ey that came with it.

Next week, a new coali­tion will be launched in Sin­ga­pore in an ef­fort to speed can­cer drug de­vel­op­ment and en­hance re­search co­op­er­a­tion be­tween the US and Chi­na, de­spite ris­ing ten­sions.

Launched by bil­lion­aire Michael Bloomberg’s eco­nom­ic fo­rum, dubbed the Bloomberg In­ter­na­tion­al Can­cer Coali­tion, the sum­mit will bring drug ex­ecs to­geth­er from the coun­tries with the two largest can­cer pop­u­la­tions in the world. The coali­tion will aim to cre­ate new can­cer drug stan­dards and cool tem­per­a­tures that have risen dur­ing the Covid-19 pan­dem­ic.

Rep­re­sen­ta­tives from sev­er­al high-pro­file drug­mak­ers will be in at­ten­dance, in­clud­ing J&J, Bay­er, Roche, No­var­tis, BeiGene, Zai Lab and aca­d­e­m­ic in­sti­tu­tions from Chi­na, the US and Eu­rope.

Some cur­rent and for­mer diplo­mats will al­so be in at­ten­dance, but rep­re­sen­ta­tives from Chi­na and its health reg­u­la­tor have not yet said whether they’ll be in Sin­ga­pore, the Fi­nan­cial Times re­port­ed Sun­day.

One diplo­mat, for­mer Aus­tralian Prime Min­is­ter and Asia So­ci­ety chief Kevin Rudd, told FT the ef­fort to lessen the pan­dem­ic-in­duced saber-rat­tling is akin to the 1970s dé­tente be­tween the US and Chi­na, which saw the coun­tries use ta­ble ten­nis as a way to thaw Cold War an­i­mosi­ties.

“The US-Chi­na re­la­tion­ship has got so bad that we at the Asia So­ci­ety have formed a view that can­cer treat­ment tri­als may well be­come the next it­er­a­tion of ping-pong diplo­ma­cy, to get this re­la­tion­ship back on the rails,” he told FT.

Rudd added that dis­agree­ments over in­tel­lec­tu­al prop­er­ty will like­ly be dis­cussed at the sum­mit.