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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; 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.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.