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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Thomas Lingelbach, Valneva CEO

Small biotech says its Covid-19 vac­cine spurs more an­ti­bod­ies than As­traZeneca’s. Will sup­ply deals come now?

In a first, a small runner-up vaccine developer says its own Covid-19 jab has induced “superior neutralizing antibody titer levels” over AstraZeneca’s AZD1222 when pitted head-to-head in a Phase III trial.

That and non-inferiority in seroconversion rate were the co-primary endpoints of the trial, which recruited 4,012 adult volunteers across the UK.

But on the exploratory endpoint of Covid-19 case counts, Valneva notes that both treatment groups saw a similar number of infections.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.