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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Like the flu vac­cine every year, the FDA could move quick­ly on a vari­ant-tar­get­ed Covid vac­cine

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.

Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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More man­u­fac­tur­ing is­sues: Fen­nec preps for sec­ond CRL for po­ten­tial hear­ing loss drug

Shares of Fennec Pharmaceuticals stock were cut almost in half early Monday as the company said manufacturing issues caused another FDA rejection of its reformulated version of sodium thiosulfate, which is intended to help kids who lose hearing due to chemo treatment.

The biotech had resubmitted an NDA for the drug to treat platinum-based, chemo-related ototoxicity in young children earlier this year. The first NDA was denied by the FDA last year, with the agency citing manufacturing issues with the biotech’s supplier.

Róbert Wessman, Alvogen CEO

Biotech bil­lion­aire Róbert Wess­man en­gi­neers $450M deal for Alvo­gen sub­sidiaries

Alvogen is handing off two of its subsidiaries to CEO Róbert Wessman and his healthcare investment firm Aztiq — who has now tied the two together in a massive biobucks deal.

In an alliance with Thailand’s PTT Group subsidiary Innobic, the two companies signed an agreement last week to buy a 100% stake in Alvogen Emerging Market Holdings Limited (AEMH) for $475 million from Alvogen, buying out shareholders such as CVC Capital Partners and Singapore’s Temasek. And now, the group is the majority shareholder of Alvogen’s former Asian subsidiary Lotus Pharmaceuticals and the only shareholder of Alvogen Malta, the owner of B2B pharma Adalvo.

Shankar Musunuri, Ocugen CEO

Ocu­gen hits an­oth­er snag in bring­ing its Bharat Biotech-part­nered Covid-19 vac­cine to the US

Back in July, Ocugen and Bharat Biotech unveiled some Phase III data suggesting their Covid-19 vaccine, Covaxin, was 77.8% effective at preventing overall disease in India. They’re now looking to launch an immuno-bridging study to see if those numbers hold up in the US — but on Friday, the FDA said not so fast.

Regulators have placed a clinical hold on the partners’ IND, Ocugen shared on Friday. Ocugen’s stock $OCGN sank 9% on the news Friday, but was up almost 7% in pre-market trading on Monday.

Covid-19 roundup: As Omi­cron spreads, African biotech re­port­ed­ly close to re­pro­duc­ing Mod­er­na's vac­cine, while WHO cre­ates pan­dem­ic pre­ven­tion body

The emergence of the Omicron variant over the holiday has reignited the focus on vaccine equity, and in its efforts to bring more shots to Africa, one South African biotech is reportedly close to reproducing Moderna’s mRNA shot.

Afrigen Biologics and Vaccines is speeding toward its pivotal trials, the Washington Post reported Sunday, though it’s doing so without Moderna’s recipe. The biotech reportedly has finished sequencing the Moderna vaccine and plans to soon compare its own recreation to Moderna’s jab.