Albert Bourla, AP

Covid-19 roundup: Al­bert Bourla says Pfiz­er PhI­II is at 23,000 pa­tients, sub­mis­sion com­ing end of Oc­to­ber

Months ago, pub­lic health of­fi­cials thought it could take sev­er­al months to prove a vac­cine works. Even when con­tin­u­al­ly high coro­n­avirus case counts in the US made tri­als eas­i­er to run, there was still con­cern about how quick­ly com­pa­nies would be able to en­roll vol­un­teers.

On Thurs­day, though, Pfiz­er CEO Al­bert Bourla dis­closed that, as of yes­ter­day, Pfiz­er had reached 23,000 vol­un­teers in the Phase III tri­al for their mR­NA Covid-19 vac­cine, a “sig­nif­i­cant num­ber” of whom have al­ready got­ten the sec­ond dose.  That would put Pfiz­er and their part­ner BioN­Tech just 7,000 pa­tients short of their tar­get and, Bourla said, in line to give an up­date on ef­fi­ca­cy by the end of Oc­to­ber.

“By the end of Oc­to­ber… we should have enough events to know if the prod­uct works or not,” Bourla said, adding they would “im­me­di­ate­ly” sub­mit for the vac­cine ap­proval. “We’ve al­ready worked on the rest of the file,” he said.

The time­line would be in line with what gov­ern­ment of­fi­cials are ev­i­dent­ly prepar­ing for. The CDC this week sent out a let­ter to states urg­ing them to pre­pare for vac­cine dis­tri­b­u­tion by Oc­to­ber 1. Those plans ap­peared de­signed for ei­ther a vac­cine from Mod­er­na or Pfiz­er. These can­di­dates, both com­posed of mR­NA, have to be kept in ul­tra-cold stor­age set­tings, mak­ing the dis­tri­b­u­tion more com­plex than for oth­er vac­cines.

Mod­er­na, the oth­er com­pa­ny with a Phase III vac­cine tri­al that has kept apace with Pfiz­er, was at 17,458 en­rollees as of last Fri­day.

Bourla al­so said that the com­pa­ny had de­vel­oped an an­tivi­ral mol­e­cule that is now in the clin­ic and would have safe­ty re­sults be­fore the end of the month. Pfiz­er has said for months that it is work­ing on an­tivi­rals, but it had not dis­closed a com­pound. A clin­i­cal tri­al list­ing for the drug, known as PF-07304814, went up ear­li­er this week.  It is a 56-per­son Phase I study.

“It could be an al­ter­na­tive for peo­ple who don’t re­spond very well to remde­sivir,” Bourla said, “or it could be in com­bi­na­tion.”

– Ja­son Mast

US says it won’t pay re­main­ing WHO dues

Fol­low­ing the an­nounce­ment that the US plans to leave the WHO in Ju­ly, gov­ern­ment of­fi­cials said Wednes­day the coun­try would not pay its re­main­ing dues to the or­ga­ni­za­tion.

The US is ex­pect­ed to with­draw on Ju­ly 6, 2021, and has re­main­ing dues of about $80 mil­lion that are owed. That mon­ey will in­stead be redi­rect­ed to­ward fund­ing oth­er Unit­ed Na­tions pro­grams, ac­cord­ing to a Reuters re­port. About $18 mil­lion re­mains from the coun­try’s oblig­a­tions from fis­cal year 2019, while the re­main­ing $62 mil­lion is from fis­cal year 2020.

Most of the mon­ey will help pay for chil­dren’s im­mu­niza­tion and flu pro­grams, and the US will con­tin­ue to sup­port WHO work in Libya and Syr­ia and on erad­i­cat­ing po­lio in Pak­istan and Afghanistan, the New York Times wrote. Amer­i­can of­fi­cials work­ing as ad­vi­sors to the WHO will al­so be with­drawn.

UN mem­bers are re­quired to give one year’s no­tice about with­drawals. About two months ago, on Ju­ly 7, Pres­i­dent Don­ald Trump for­mal­ly no­ti­fied the WHO that the US would be leav­ing and claimed that it had be­come a mouth­piece for Chi­na dur­ing the Covid-19 pan­dem­ic.

His­tor­i­cal­ly, the US has been the biggest boost­er of the WHO, help­ing found the or­ga­ni­za­tion af­ter World War II. Joe Biden, the De­mo­c­ra­t­ic pres­i­den­tial nom­i­nee, has said he will re-en­ter the WHO should he win the No­vem­ber elec­tion. — Max Gel­man

CDC di­rec­tor tells states to be ready for vac­cine dis­tri­b­u­tion by Nov. 1

Drug­mak­ers aren’t the on­ly ones fac­ing pres­sure to hur­ry out a vac­cine. Last week, CDC di­rec­tor Robert Red­field penned a let­ter to state gov­er­nors, re­quest­ing that vac­cine dis­tri­b­u­tion sites be ful­ly op­er­a­tional by Nov. 1.

Red­field urged gov­er­nors to fast-track per­mits and li­cens­es, ac­cord­ing to a Mc­Clatchy re­port. “The nor­mal time re­quired to ob­tain these per­mits presents a sig­nif­i­cant bar­ri­er to the suc­cess of this ur­gent pub­lic health pro­gram,” the let­ter read.

“CDC ur­gent­ly re­quests your as­sis­tance in ex­pe­dit­ing ap­pli­ca­tions for these dis­tri­b­u­tion fa­cil­i­ties … and, if nec­es­sary, asks that you con­sid­er waiv­ing re­quire­ments that would pre­vent these fa­cil­i­ties from be­com­ing ful­ly op­er­a­tional by No­vem­ber 1, 2020,” it con­tin­ued.

The Aug. 27 re­quest came on the same day that pres­i­dent Don­ald Trump gave a na­tion­al speech promis­ing a “safe and ef­fec­tive” vac­cine with­in the next four months. And ru­mors have spread that mem­bers of the Trump ad­min­is­tra­tion told De­mo­c­ra­t­ic leader Nan­cy Pelosi a vac­cine can­di­date could get emer­gency ap­proval as ear­ly as Sep­tem­ber, and that it would like­ly be As­traZeneca’s.

Dis­trib­u­tors are brac­ing for sig­nif­i­cant chal­lenges ahead, in­clud­ing the avail­abil­i­ty of cold stor­age fa­cil­i­ties to keep vac­cines sta­ble. Some mR­NA can­di­dates must be stored at tem­per­a­tures as low as -80 de­grees Cel­sius.

Mod­er­na, which ex­pects to com­plete Phase III en­roll­ment for its vac­cine tri­al this month, said its can­di­date would need to be stored long-term at -20 de­grees Cel­sius. BioN­Tech and Pfiz­er’s can­di­date re­quires long-term stor­age at -70 de­grees Cel­sius. Last week, the com­pa­nies an­nounced they’ve en­rolled near­ly half of 30,000 ex­pect­ed Phase III par­tic­i­pants.

FDA com­mis­sion­er Stephen Hahn has vowed vac­cine ap­proval will be strict­ly da­ta-dri­ven. “We at FDA do not per­mit pol­i­tics to en­ter in­to our sci­en­tif­ic de­ci­sions,” he tweet­ed last week.

But the com­mis­sion­er is fac­ing heat for mis­lead­ing com­ments he made about the ef­fi­ca­cy of con­va­les­cent plas­ma as a Covid-19 treat­ment. Days lat­er, he an­nounced that a vac­cine ad­vi­so­ry com­mit­tee meet­ing will take place on Oct 22.

“If you are mak­ing a de­ci­sion about the vac­cine, you’d bet­ter be sure you have very good ev­i­dence that it is both safe and ef­fec­tive,” Fau­ci said in an in­ter­view with KHN on Tues­day. “I’m not con­cerned about po­lit­i­cal pres­sure.” — Nicole De­Feud­is 

Steroids re­duce mor­tal­i­ty by 20% in se­vere Covid-19 cas­es, re­searchers say

A new analy­sis of sev­en in­ter­na­tion­al tri­als is point­ing to­ward steroids as a po­ten­tial­ly ef­fec­tive treat­ment for the sick­est of Covid-19 pa­tients.

The study, pub­lished in JA­MA on Wednes­day, pooled da­ta from tri­als uti­liz­ing three types of cor­ti­cos­teroids in more than 1,700 pa­tients in in­ten­sive care. Re­searchers found that the risk of death was re­duced by 20% and as­sert­ed that the drugs should be the first-line treat­ment for se­vere­ly ill pa­tients.

“The meta-analy­sis in­di­cates that ad­min­is­tra­tion of steroids is clear­ly as­so­ci­at­ed with ben­e­fit among crit­i­cal­ly ill pa­tients with COVID-19, al­though the ex­act thresh­old at which an in­di­vid­ual pa­tient should be pre­scribed cor­ti­cos­teroids re­mains un­clear,” re­searchers wrote in a re­lat­ed ed­i­to­r­i­al.

Late Wednes­day, the WHO up­dat­ed its treat­ment guid­ance to make a “strong rec­om­men­da­tion” for the use of low dose hy­dro­cor­ti­sone, dex­am­etha­sone and methyl­pred­nisolone in crit­i­cal cas­es. The pa­per did not find that the drugs had any ef­fect on milder Covid-19 pa­tients.

On­ly Gilead’s remde­sivir has proven to be ef­fec­tive in treat­ing se­vere Covid-19 cas­es, though its ben­e­fits thus far have been lim­it­ed.

Wednes­day’s pa­per fol­lows stud­ies from Ox­ford re­searchers back in June in­di­cat­ing that dex­am­etha­sone could re­duce the risk of mor­tal­i­ty in such cas­es. The steroid had shown by it­self a one-third re­duc­tion among pa­tients on ven­ti­la­tors and a one-fifth re­duc­tion in those re­ceiv­ing oxy­gen.

Steroids can cause some side ef­fects such as open­ing the body to oth­er in­fec­tions, how­ev­er, and the WHO’s new guid­ance said that those risks re­in­force that the drugs should not be used in milder cas­es. — Max Gel­man

Chi­na ex­pands emer­gency vac­cine use to avi­a­tion in­dus­try

First it’s the mil­i­tary. Then came of­fers for state em­ploy­ees dis­patched over­seas, as well as med­ical work­ers and bor­der con­trol of­fi­cers. Now, Chi­na is hand­ing out ex­per­i­men­tal coro­n­avirus vac­cines to those in the avi­a­tion in­dus­try.

The move is an ex­pan­sion of the emer­gency use pro­gram that be­gan in Ju­ly, whose stat­ed goal is to boost the im­mu­ni­ty of high-risk groups to pre­vent a new wave of in­fec­tions.

Chi­na’s avi­a­tion reg­u­la­tor has told air­lines, air­ports, Chi­na Na­tion­al Avi­a­tion Fu­el Group and Trav­el­Sky Tech­nol­o­gy that their front­line work­ers can ac­cess a vac­cine can­di­date on a vol­un­tary ba­sis, Reuters re­port­ed cit­ing a no­tice.

It’s un­clear which vac­cines the work­ers will be giv­en. Pre­vi­ous re­ports of vac­ci­na­tion cam­paigns at state-owned en­ter­pris­es al­so trig­gered eth­i­cal con­cerns about con­sent, as ex­perts be­lieve em­ploy­ees may feel pres­sured to say yes to a vac­cine de­spite lack of safe­ty and ef­fi­ca­cy da­ta from large-scale tri­als.

Four vac­cine can­di­dates from Chi­nese de­vel­op­ers have en­tered Phase III — all over­seas — so far. Among them, CanSi­no’s ade­n­ovirus-based shot is au­tho­rized for mil­i­tary use while Sino­vac and Sinopharm both have vac­cines cleared for ad­min­is­tra­tion among high-risk groups. — Am­ber Tong

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Years af­ter a ma­jor tri­al set­back, No­var­tis switch­es gears with SMA drug. This time they're try­ing it for Hunt­ing­ton's

Four years after a Phase I/II setback in spinal muscular atrophy (SMA), Novartis is hoping its drug branaplam will find more success in a new neurological indication: Huntington’s disease.

The decision was announced a year after the head of research, Jay Bradner, said he did not see a “big opportunity” in SMA, according to Reuters. Novartis says it has preclinical data showing that branaplam reduces levels of mutant huntingtin protein, and SMA data showing patients on the drug had reductions in huntingtin mRNA. The FDA gave branaplam their orphan drug designation, and Novartis plans to move forth with a Phase IIb trial next year.

Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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Glax­o­SmithK­line's vac­cines group aims for a first as it kicks off PhI­II RSV stud­ies

One of GlaxoSmithKline’s big projects at its global vaccine R&D center in Rockville, MD is set to enter Phase III after passing early-stage tests with flying colors.

Eyeing the wide-open respiratory syncytial virus (RSV) space, GSK is pushing two different vaccine candidates: GSK3888550A is designed to confer protection to infants via maternal immunization, while GSK3844766A is meant for the elderly.

Pur­due Phar­ma signs guilty plea, preps $8B+ set­tle­ment on Oxy con­tro­ver­sy — re­port; Flag­ship brings in a comms chief

Purdue Pharma may soon be signing off on a guilty plea and an $8 million-plus settlement to wrap up its controversial role distributing OxyContin.

The AP has the breaking story this morning.

Purdue filed for bankruptcy last year, along with Insys and followed by Mallinckrodt, as it navigated its way through a blizzard of litigation surrounding Oxy, which triggered an epidemic of abuse around the country.

UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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