Eli Lil­ly launch­es PhI­II JAK study, aim­ing for the first drug to low­er mor­tal­i­ty in Covid-19

Soon af­ter the NIH an­nounced in late April that Eli Lil­ly’s JAK in­hibitor baric­i­tinib would be the sec­ond drug test­ed in the tri­al that had proven remde­sivir ef­fec­tive, doc­tors around the world be­gan telling Lil­ly that that wouldn’t be enough.

Since the ear­ly days of the pan­dem­ic, the In­di­anapo­lis phar­ma had heard from doc­tors in Italy, Spain and else­where who, fac­ing hos­pi­tals full of pa­tients with a dis­ease with no known treat­ment, used the JAK in­hibitor — known com­mer­cial­ly as the rheuma­toid arthri­tis drug  Olu­mi­ant — off-la­bel. The doc­tors want­ed to know con­clu­sive­ly if it worked. But the NIH tri­al could on­ly tell them if, when com­bined with remde­sivir, it worked bet­ter than remde­sivir alone. And then on­ly in the more se­vere pa­tients.

Pa­trik Jon­s­son

“We de­cid­ed it’s our oblig­a­tion,” Eli Lil­ly Bio-Med­i­cines Pres­i­dent Pa­trik Jon­s­son told End­points News. “For sci­en­tif­ic rea­sons but most im­por­tant­ly for health­care providers and for pa­tients, we need­ed to un­der­stand the over­all ef­fects of Olu­mi­ant/baric­i­tinib alone in treat­ing Covid-19.”

Lil­ly is now launch­ing their own Phase III, 400-per­son study to test whether baric­i­tinib alone can beat place­bo in treat­ing Covid-19. Spread across 15 sites in 4 coun­tries, the tri­al will test the idea that the drug not on­ly has po­ten­tial to man­age the cy­tokine storms that af­flict late-stage pa­tients, but al­so treat the dis­ease in its mild to mod­er­ate man­i­fes­ta­tions.

Un­like some oth­er ma­jor Covid-19 tri­als, in­clud­ing most no­tably the first part of the NIH study and sev­er­al Gilead ran on remde­sivir, the tri­al’s pri­ma­ry end­point won’t be about time to re­cov­ery or how symp­toms im­prove on an 8-point scale. In­stead, the ques­tion will be sim­ple: At day 28, is there a sig­nif­i­cant­ly few­er num­ber of pa­tients on the drug arm who have died or gone to ven­ti­la­tion than in the place­bo arm?

“Since the com­mu­ni­ty got the da­ta on remde­sivir in the be­gin­ning of May, we are set­ting the bar high­er,” Jonn­son said. “We need to add in­cre­men­tal val­ue.”

The new Lil­ly tri­al joins a throw-any­thing-against-the-wall now cov­ered in tra­di­tion­al Chi­nese and In­di­an med­i­cines, im­mune block­ers and im­mune boost­ers, an­ti-co­ag­u­lants, and an­tivi­rals of myr­i­ad ori­gins. Clin­i­cal­tri­als.gov now lists 1,211 dif­fer­ent in­ter­ven­tion­al Covid-19 tri­als.

Still, re­searchers say there’s rea­son to be­lieve that baric­i­tinib has bet­ter odds than oth­ers. It was first iden­ti­fied as a po­ten­tial treat­ment in Feb­ru­ary by the British biotech Benev­o­lent AI as part of a ma­chine learn­ing-based drug screen.

Vin­cent Mar­coni

“Baric­i­tinib, be­ing a JAK in­hibitor, has some ad­van­tages on some of the oth­er cy­tokine agents,” Vin­cent Mar­coni, an in­fec­tious dis­ease spe­cial­ist at Emory Uni­ver­si­ty, told End­points.

Like the Roche drug IL-6 block­ing drug Actem­ra — which has shown po­ten­tial in ear­ly stud­ies — baric­i­tinib blocks some of the cy­tokines, or im­mune sig­nals, that can lead to an over­ac­tive in­flam­ma­to­ry re­sponse in some pa­tients. But un­like IL-6 block­ers, Mar­coni said, baric­i­tinib blocks sev­er­al im­mune path­ways as op­posed to just one.

“The hope with a sin­gle cy­tokine ther­a­py is that maybe you can get the crit­i­cal one and that’s all that’s need­ed, and the oth­er ones don’t play much of a role. We don’t know the an­swer to the yet,” Mar­coni said. “But with JAK-STAT in­hibitors like baric­i­tinib, we’re re­al­ly tar­get­ing mul­ti­ple of these cy­tokine path­ways. I think that’s one of the main at­trac­tive ra­tio­nales.”

With virus-neu­tral­iz­ing an­ti­bod­ies now en­ter­ing hu­man test­ing — in­clud­ing two from Eli Lil­ly — to great med­ical at­ten­tion, Mar­coni said he could imag­ine a fu­ture where sev­er­al of the most ef­fec­tive ther­a­pies were used in com­bi­na­tion, as in HIV treat­ments.

Any coro­n­avirus study will fluc­tu­ate with the case counts in tri­al site cities, but Lil­ly is hop­ing to have re­sults by Sep­tem­ber. The NIH hasn’t an­nounced a time­line, but the com­pa­ny said it is al­ready more than half-en­rolled.

Pa­tients in the tri­al will still be able to take remde­sivir if their doc­tors pre­scribe it, al­though pa­tients would not nec­es­sar­i­ly fit cri­te­ria for both, said Patrick Mil­li­gan, an in­fec­tious dis­ease spe­cial­ist at the Com­mu­ni­ty Health Net­work in In­di­anapo­lis, one of the study sites. Al­though guid­ance for remde­sivir can vary state to state and even hos­pi­tal to hos­pi­tal, it is gen­er­al­ly giv­en to lat­er-stage pa­tients.

Mil­li­gan said his hos­pi­tal has giv­en baric­i­tinib to Covid-19 pa­tients since the ear­ly days of the pan­dem­ic and the pa­tients who re­ceived it seemed to do bet­ter than those that got Actem­ra. But the re­sults were hard to parse; the pa­tients who got Actem­ra were gen­er­al­ly al­ready in worse con­di­tion.

”This is all anec­do­tal. It’s use­ful. If that’s the da­ta you have, that’s fine,” he told End­points. But now they were join­ing the study “to hope­ful­ly help get some de­fin­i­tive an­swers.”

So­cial: Dar­ron Cum­mings, AP Im­ages

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

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Emma Walmsley, GlaxoSmithKline CEO (Kevin Dietsch/Pool via CNP/Alamy)

Glax­o­SmithK­line hus­tles the 7th PD-1 past the fin­ish line with Jem­per­li. But how big will up­take be?

Everything came up sevens for GlaxoSmithKline on Thursday as the pharma notched the seventh PD-1 approval seven years after the first such drugs were OK’ed in Keytruda and Opdivo. But will it bring GSK good fortune?

The FDA granted accelerated approval to dostarlimab, to be branded Jemperli, to treat recurrent or advanced endometrial cancer in a specific subset of patients following platinum-based chemo. It’s a drug that came to GSK through its buyout of Tesaro, which it snapped up for $5.1 billion back in December 2018.

JP Gabriel, Ocugen

JP Gabriel watched from the bleach­ers as the pan­dem­ic raged. Now head of sup­ply chain at Ocu­gen, he's ready to bat

The world was in the middle of the most pressing public health risk his generation had ever seen, and JP Gabriel felt like he was sitting on the sidelines. As a VP of biologics and mRNA manufacturing at Ultragenyx, Gabriel watched from the sidelines as players like Pfizer/BioNTech and Moderna used mRNA tech to chase their own Covid-19 vaccines.

This month, Gabriel got the chance to get his hands dirty against the pandemic — but it won’t be with mRNA.

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Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.