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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Work taking place in the clean rooms at Vor (Credit: Vor)

Vor Bio opts to keep man­u­fac­tur­ing op­er­a­tions in-house for de­vel­op­ing stem cell, CAR-T ther­a­pies

While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

Aim­ing for fourth nod, Sarep­ta files an­oth­er DMD gene ther­a­py to FDA; Ax­some head­ed to­ward mi­graine re­sub­mis­sion

Sarepta Therapeutics has filed the data needed for an FDA accelerated approval, which would be the biotech’s fourth if granted by the agency.

The biotech has yet to complete confirmatory trials for those first three conditional nods. The filing for its fourth Duchenne muscular dystrophy treatment, disclosed Thursday, is not a surprise. Sarepta said in late-July it would do so after releasing positive results for the Roche-partnered gene therapy.

Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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Aligos co-founders Leonid Beigelman (L) and Lawrence Blatt

Ali­gos co-founders shoot back at J&J IP com­plaint with one of their own al­leg­ing fraud

This story goes all the way back to 2014.

In November of 2014, Johnson & Johnson acquired Alios BioPharma, an infectious disease biotech that was co-founded by Lawrence Blatt and Leonid Beigelman.

Following J&J’s 2014 acquisition, Blatt and Beigelman would become employees at J&J’s Janssen arm, with Blatt being the global head of infectious diseases and vaccines and Beigelman being Janssen’s VP of medicinal chemistry. But Blatt and Beigelman left Janssen in 2017, starting Aligos one year later.

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