Covid-19 roundup: Carl June on hav­ing Covid-19 and his plan to treat it; NIH preach­es cau­tion; 2 new vac­cines en­ter clin­ic

Carl June had Covid-19. Now he’s try­ing to fig­ure out how the world can treat it.

In an in­ter­view with the Philadel­phia In­quir­er, the CAR-T pi­o­neer and Uni­ver­si­ty of Penn­syl­va­nia im­mu­nol­o­gist re­vealed that he had been sick with a “mild to mod­er­ate” case of the virus for 3 weeks. Now re­cov­ered, he is try­ing to do­nate his plas­ma and he has some thoughts about how the bio­med­ical com­mu­ni­ty should pur­sue new treat­ments.

Promis­ing ex­per­i­men­tal treat­ments ex­ist, he said, but they are be­ing pur­sued in an in­ef­fi­cient man­ner, with hun­dreds of dif­fer­ent tri­als for ther­a­pies rang­ing from holis­tic reme­dies to ex­per­i­men­tal an­tivi­rals to re­pur­posed ap­proved drugs. Many of those tri­als are test­ing the same treat­ments.

“There are many re­dun­dant tri­als, not pri­or­i­tized based on sci­ence but on com­pa­nies’ port­fo­lios,” June told the In­quir­er. “They use pa­tients up. It doesn’t al­lo­cate ba­sic re­sources wise­ly.”

For ex­am­ple, he named the more than a dozen tri­als be­ing run on Actem­ra, the Roche drug that blocks the im­mune sig­nal IL-6. June orig­i­nal­ly used the drug in 2013 to suc­cess­ful­ly treat the over­ac­tive im­mune re­sponse — called cy­tokine storms — that emerged as a com­pli­ca­tion of his CAR-T can­cer treat­ment. Doc­tors be­lieve cy­tokine storms, prompt­ed by the virus but re­main­ing even af­ter the virus is large­ly gone, are caus­ing some of the life-threat­en­ing symp­toms seen in some Covid-19 pa­tients.

June said he was con­fi­dent Actem­ra would be ef­fec­tive, but said it was too ex­pen­sive to be the panacea for a glob­al pan­dem­ic. “They can’t af­ford it in In­dia,” he said. “They need some­thing cheap.”

So June is try­ing to or­ga­nize a tri­al for a dif­fer­ent im­mune-sup­press­ing drug: cy­closporine. The com­pound, used to pre­vent re­jec­tion in or­gan trans­plant pa­tients, is a gener­ic and al­ready ex­ists in large sup­ply, mak­ing it an ide­al can­di­date for the de­vel­op­ing world. In a tri­al, it would be giv­en to pa­tients when they are first hos­pi­tal­ized to see if it pre­vents an im­mune over­re­ac­tion. The Penn ethics re­view board is cur­rent­ly re­view­ing the tri­al.

Both drugs, though, have the po­ten­tial to back­fire, turn­ing down the im­mune sys­tem’s abil­i­ty to fight the virus it­self. Roche said to­day they ex­pect re­sults on Actem­ra in June. — Ja­son Mast

Ox­ford’s Covid-19 vac­cine pro­gram to en­ter PhI to­mor­row

An­oth­er Covid-19 vac­cine will en­ter the clin­ic to­mor­row.

A group at Ox­ford Uni­ver­si­ty led by im­mu­nol­o­gist Sarah Gilbert and backed by the UK gov­ern­ment will be­gin test­ing their vac­cine can­di­date in health vol­un­teers, with the hope of ex­per­i­men­tal­ly vac­ci­nat­ing 500 peo­ple by the mid­dle of May. The vac­cine, made of re­com­bi­nant DNA and de­liv­ered through an ade­n­ovirus, has been in de­vel­op­ment since short­ly af­ter the se­quence of the nov­el coro­n­avirus be­came avail­able in ear­ly Jan­u­ary.

The UK gov­ern­ment has made £20 mil­lion (rough­ly $25 mil­lion) avail­able to back the ef­fort, Sec­re­tary of State for Health & So­cial Care Matt Han­cock an­nounced this week. They al­so made £22.5 mil­lion avail­able for an RNA vac­cine project at the Im­pe­r­i­al Col­lege of Lon­don.

Gilbert, who has pre­vi­ous­ly worked on vac­cines for out­breaks such as SARS and Zi­ka, has laid out an an ag­gres­sive time­line for the vac­cine, telling The Lancet last week that in a best-case sce­nario she hoped to have both Phase III ef­fi­ca­cy da­ta on 5,000 vol­un­teers and the abil­i­ty to man­u­fac­ture large dos­es by the fall, with the caveat that “these best-case time­frames are high­ly am­bi­tious and sub­ject to change.”

The fall is al­so when Mod­er­na — which built the first vac­cine to en­ter clin­i­cal tri­als — has said they could have a vac­cine ready for emer­gency use, al­though the com­pa­ny has said it’s un­clear if those would be giv­en as part of a tri­al, un­der com­pas­sion­ate use, or a dif­fer­ent pro­to­col.

J&J, which has a $1 bil­lion part­ner­ship with BAR­DA, and CanSi­no, the lead­ing Chi­nese Covid-19 vac­cine pro­gram, al­so use ade­n­ovirus-based vac­cines. — Ja­son Mast

NIH guide­lines preach cau­tion, pa­tience on treat­ments

The NIH has post­ed its of­fi­cial treat­ment guide for Covid-19, and the ma­jor take­away is a mes­sage many sci­en­tists have been preach­ing: Wait for more ev­i­dence be­fore lean­ing one way or an­oth­er. De­vel­oped by a pan­el of ex­perts, many of whom are front­line clin­i­cians, the “liv­ing doc­u­ment” cov­ers two wide­ly-dis­cussed cat­e­gories of ther­a­pies: an­tivi­rals, which tar­get the virus, and host mod­i­fiers and im­mune-based ther­a­pies, which may tar­get the pa­tient.

In the an­tivi­ral realm, the pan­el con­clud­ed that there are in­suf­fi­cient clin­i­cal da­ta to rec­om­mend ei­ther for or against the three hottest drugs: the an­ti­malar­i­al drugs chloro­quine and hy­drox­y­chloro­quine, or Gilead’s re­pur­posed Ebo­la drug remde­sivir.

The guide­lines stand in sharp con­trast with Pres­i­dent Trump’s en­thu­si­as­tic en­dorse­ment of hy­drox­y­chloro­quine and chloro­quine. Every turn of events sur­round­ing the pair of drugs — which are al­so tak­en by pa­tients with au­toim­mune dis­eases such as lu­pus and rheuma­toid arthri­tis — have elicit­ed strong opin­ions, from the FDA’s con­tro­ver­sial emer­gency use au­tho­riza­tion to the re­sults from the small stud­ies con­duct­ed thus far.

Out­side of a clin­i­cal tri­al, the NIH ex­perts sug­gest physi­cians don’t pre­scribe hy­drox­y­chloro­quine plus azithromycin for fear of tox­i­c­i­ty. The same ad­vice ap­plies to HIV pro­tease in­hibitors such as lopinavir/ri­ton­avir “be­cause of un­fa­vor­able phar­ma­co­dy­nam­ics and neg­a­tive clin­i­cal tri­al da­ta.”

Im­mune-based ther­a­pies didn’t of­fer clear­er an­swers. The pan­el sim­i­lar­ly con­clud­ed it’s too ear­ly to say ei­ther yay or nay on con­va­les­cent plas­ma, hy­per­im­mune im­munoglob­u­lin, IL-6 in­hibitors or IL-1 in­hibitors. As for in­ter­fer­ons and JAK in­hibitors — a class that en­com­pass­es Eli Lil­ly’s Olu­mi­ant, now be­ing test­ed in pa­tients — they’re not rec­om­mend­ed un­less in a tri­al set­ting. — Am­ber Tong

Roche’s Sev­erin Schwan lam­basts an­ti­body test ‘dis­as­ter’

Roche’s mild man­nered CEO has some harsh words re­served for the de­vel­op­ers be­hind some of the an­ti­body tests cur­rent­ly on the mar­ket. “It’s a dis­as­ter,” Schwan was cit­ed as say­ing on a con­fer­ence call.

Hav­ing got­ten the green light ear­ly to de­ploy its coro­n­avirus tests, the Swiss phar­ma gi­ant is plan­ning to re­lease an an­ti­body test in May. By an­a­lyz­ing peo­ple’s blood and de­tect­ing any an­ti­bod­ies against SARS-CoV-2, the di­ag­nos­tic is sup­posed to tell whether they have ever been in­fect­ed.

A num­ber of such tests, al­so known as sero­log­i­cal tests, have al­ready been rolled out to the mar­ket. They come from about 90 com­pa­nies, many based in Chi­na, and were au­tho­rized be­fore get­ting re­viewed. Mul­ti­ple news out­lets have re­port­ed that ex­perts are con­cerned about their ac­cu­ra­cy, ques­tion­ing whether the FDA — chid­ed for its slow re­sponse to the nasal swab tests — set the qual­i­ty stan­dards too low this time around in pur­suit of speed.

“These tests are not worth any­thing, or have very lit­tle use,” Schwan said, ac­cord­ing to Reuters. “Some of these com­pa­nies, I tell you, this is eth­i­cal­ly very ques­tion­able to get out with this stuff.” — Am­ber Tong

BioN­Tech, Pfiz­er moves in­to hu­man tri­al with mR­NA vac­cine can­di­date in Ger­many

BioN­Tech and Pfiz­er have se­cured ap­proval from Ger­man au­thor­i­ties to be­gin test­ing its four vac­cine can­di­dates in hu­mans. The Phase I/II tri­al will en­roll 200 healthy vol­un­teers to find the op­ti­mal dose.

Here’s an overview of the BNT162 pro­gram:

Two of the four vac­cine can­di­dates in­clude a nu­cle­o­side mod­i­fied mR­NA (mod­R­NA), one in­cludes a uri­dine con­tain­ing mR­NA (uR­NA), and the fourth vac­cine can­di­date uti­lizes self-am­pli­fy­ing mR­NA (saR­NA). Each mR­NA for­mat is com­bined with a lipid nanopar­ti­cle (LNP) for­mu­la­tion. The larg­er spike se­quence is in­clud­ed in two of the vac­cine can­di­dates, and the small­er op­ti­mized re­cep­tor bind­ing do­main (RBD) from the spike pro­tein is in­clud­ed in the oth­er two can­di­dates. The RBD-based can­di­dates con­tain the piece of the spike that is thought to be most im­por­tant for elic­it­ing an­ti­bod­ies that can in­ac­ti­vate the virus.

The part­ners are al­so await­ing reg­u­la­to­ry de­ci­sions in the US, while BioN­Tech is work­ing with Fo­s­un to be­gin tri­als in Chi­na. — Am­ber Tong

San Diego biotech tests in­ter­sti­tial lung dis­ease drug for se­vere Covid-19 pa­tients

As the sever­i­ty and dan­ger of res­pi­ra­to­ry com­pli­ca­tions among Covid-19 pa­tients be­come clear, aTyr is join­ing the long line of bio­phar­ma com­pa­nies pitch­ing their an­ti-in­flam­ma­to­ry drugs to the fight. The San Diego-based biotech has re­cent­ly come up with pos­i­tive safe­ty da­ta in a Phase Ib/IIa study in­volv­ing pa­tients with pul­monary sar­coido­sis and will now launch a Phase II study in se­vere Covid-19 pa­tients.

The the­o­ry is that ATYR1923 down­reg­u­lates T-cell re­spons­es, there­by damp­en­ing the in­flam­ma­to­ry cy­tokine and chemokine sig­nal­ing. The drug can al­so im­prove lung func­tion, aTyr added, based on an­i­mal mod­els.

The tri­al will en­roll 30 pa­tients in the US, with 10 pa­tients each ran­dom­ized to take 1mg/kg, 3mg/kg or place­bo. — Am­ber Tong

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

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.