FDA pan­el of­fers a wa­ver­ing thumbs up for Eli Lil­ly's 2 mg baric­i­tinib, thumbs down on 4 mg

A large pan­el of out­side rheuma­toid arthri­tis ex­perts gath­ered at the FDA to dis­cuss Eli Lil­ly’s $LLY con­tro­ver­sial re-ap­pli­ca­tion for an ap­proval of baric­i­tinib, vot­ing in lop­sided fa­vor of the ef­fi­ca­cy and safe­ty of the 2 mg dose of the rheuma­toid arthri­tis drug, but turned their thumbs down on the 4 mg dose.

Ten vot­ed in fa­vor of the risk/ben­e­fit bal­ance of the 2 mg dose, 5 against. The num­bers were re­versed for the 4 mg, falling 10 against and 5 in fa­vor.

Jose Sch­er

These ex­pert votes hinged on a con­sid­er­able amount of con­fu­sion and un­cer­tain­ty, though, which sev­er­al mem­bers were quick to ac­knowl­edge.

Said one mem­ber who vot­ed yes on the ad­e­qua­cy of the safe­ty da­ta of the 2 mg dose: “This whole thing is a house of cards and I could have gone ei­ther way.”

An­oth­er: ”My best guess is yes.”

Er­i­ca Brit­tain: “I vot­ed yes, I could have def­i­nite­ly vot­ed no.”

“We still don’t have enough da­ta,” said one mem­ber who vot­ed in fa­vor of the ad­e­qua­cy of the 2 mg dose.

“I would urge the spon­sor to get as much da­ta as pos­si­ble on the safe­ty side,” com­ment­ed com­mit­tee chair Jose Sch­er, who vot­ed against both the 2 mg and 4 mg dos­es based on in­ad­e­quate safe­ty da­ta.

That all could emerge as a ma­jor headache for Eli Lil­ly and its part­ners at In­cyte $IN­CY, as the com­pa­ny wants to start treat­ment-re­sis­tant pa­tients at 4 mg and then ta­per down to 2 mg if they sta­bi­lize their dis­ease.

Lil­ly’s shares ini­tial­ly dropped 3% in ear­ly trad­ing Tues­day, then man­aged to climb back up in­to the green, bare­ly. In­cyte shares, though, are still down 5% in mid-morn­ing trad­ing.

The pan­el dis­cus­sion in­clud­ed a me­an­der­ing se­ries of com­ments, with some voic­es sup­port­ing an ap­proval to of­fer a new op­tion for pa­tients and a few flag­ging some se­ri­ous safe­ty is­sues and oth­ers un­cer­tain just what was demon­strat­ed by the da­ta on dis­play.

On one point, the ad­vi­so­ry com­mit­tee found clear con­sen­sus around ef­fi­ca­cy. By a vote of 14 to 1 they con­clud­ed that there was clear ev­i­dence of the “sub­stan­tial ev­i­dence” that backed the drug’s ef­fi­ca­cy, with a unan­i­mous vote in fa­vor of ef­fi­ca­cy as a sec­ond-line ther­a­py af­ter pa­tients had failed on their front­line drug.

Much of the dis­cus­sion, though, cen­tered on the safe­ty of the drug, where reg­u­la­tors raised some of their most se­ri­ous ob­jec­tions to the drug, with a star­tling sig­nal on throm­boem­bolism.

One com­mit­tee mem­ber not­ed a dis­cus­sion con­cern­ing whether rheuma­tol­o­gists are used to look­ing for and mon­i­tor­ing for ad­verse events. But, he added, “rheuma­tol­o­gists do not typ­i­cal­ly look for throm­boem­bol­ic events, that’s not on the list of things that are tra­di­tion­al­ly watched for.”

There was a con­sid­er­able dis­cus­sion whether the com­mit­tee had the da­ta need­ed to make a con­clu­sion on the drug’s safe­ty, par­tic­u­lar­ly when it came to the 2 mg dose. 

“None of these stud­ies are pow­ered to look for rare events,” said Sch­er, high­light­ing stud­ies that weren’t pow­ered to de­ter­mine the risk of throm­boem­bolisms, or blood clots, and not­ing that there was con­sid­er­able con­fu­sion about the da­ta and the con­clu­sions that could be drawn from them — par­tic­u­lar­ly re­lat­ing to the 2 mg dose, where the da­ta were lack­ing.

Baric­i­tinib is a re­mark­able test case for the FDA. Re­ject­ed in 2017 in a stun­ning set­back for a drug that had been billed as a block­buster in the mak­ing, the agency re­versed course and al­lowed Lil­ly to re­file for an ap­proval as a sec­ond-line ther­a­py with­out the added da­ta that had been in­sist­ed on. The agency’s re­view makes clear that while Eli Lil­ly in­ves­ti­ga­tors pro­vid­ed more in­for­ma­tion, none of it ad­dressed their core con­cerns, es­pe­cial­ly re­gard­ing a high­er rate of throm­bo­sis that ap­peared for the first time in the field.

FDA re­view­ers dis­agreed on the da­ta of­fered for the 2 mg and 4 mg dos­es, with some will­ing to wave it through and oth­ers not­ing that the study da­ta for the 2 mg nev­er pro­vid­ed suf­fi­cient in­for­ma­tion for a de­ci­sion on safe­ty and ef­fi­ca­cy. There was al­so no con­sis­tent da­ta to back up the 4 mg dose over the 2 mg dose, ac­cord­ing to reg­u­la­tors. 

Even if it gets an ap­proval now, Lil­ly is go­ing to have an up­hill fight against Pfiz­er’s Xel­janz (to­fac­i­tinib), the first JAK in­hibitor to make it to the mar­ket — with­out the harsh FDA crit­i­cism or is­sues with throm­bo­sis that promise to cap­size Lil­ly’s launch.

Why of­fer an ap­proval now if there are oth­er drugs on the mar­ket that could do as well or bet­ter? And if it is ap­proved, will this drug be re­served for last-chance op­por­tu­ni­ties?

“We know we didn’t make your lives any eas­i­er,” said Sch­er as he turned at the end to the FDA’s rep­re­sen­ta­tives.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

Tillman Gerngross, Adagio Therapeutics CEO

An­ti­body leg­end Till­man Gern­gross is el­bow­ing his way in­to the Covid-19 R&D cru­sade: 'I don’t see this end­ing any­time soon'

One of the most influential — and outspoken — scientists at work in the field of antibody discovery is jumping into the frenzied race to create new therapeutics to treat and prevent Covid-19. And he’s operating with the conviction that the current outbreak now once again spreading like wildfire will create plenty of demand for what he has in mind.

Dartmouth professor and Adimab CEO Tillman Gerngross tells me he’s raised $50 million from a group of close VCs to spin out a new company — Adagio Therapeutics — with a full C-suite team assembled to hire up a staff and keep rolling toward the clinic.

Endpoints Premium

Premium subscription required

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

Source: Shutterstock

Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Mer­ck KGaA takes its I/O op­tion on F-star Ther­a­peu­tics; Nephron spends $215M, eye­ing spot in Covid-19 vac­cine chain

→Merck KGaA has taken an early option on an immuno-oncology program developed at F-star Therapeutics. This is their second option in the collaboration. And they added a pair of preclinical discovery programs to the alliance as well.

Any biotech going public these days wouldn’t feel right if they didn’t upsize the offering. And that’s just what Phase I biotech Pandion Therapeutics did. The autoimmune company is now selling 7 million shares, a 1.5 million share bump, for $16 to $18 a share.

GSK’s Shin­grix leader Guil­laume Pfe­fer has jumped on board Flag­ship to helm a biotech hy­brid as Afeyan’s lat­est CEO-part­ner

After spending 4 years in a senior post with GlaxoSmithKline’s star team positioning Shingrix for a blockbuster approval, Guillaume Pfefer is headed back to the biotech world — in style.

Pfefer has signed on to join Noubar Afeyan’s busy group of partners at Flagship, and he’s taking the helm of an upstart — which today is being merged with another Flagship startup — with some grand plans of its own. The announcement this morning notes that Pfefer will run Kintai Therapeutics, one of the grads of the Flagship labs.

Donald Trump and Anthony Fauci (AP Images)

Covid-19 roundup: Rus­sia hack­ers tar­get US, UK vac­cine and drug re­searchers; Fau­ci fires back at White House cam­paign to un­der­mine him

Russia has tried to steal a Covid-19 vaccine and therapeutics researcher from pharmaceutical and academic institutions in the US, UK and Canada, Britain’s National Cyber Security Centre said Thursday.

The NCSC said that hacking attempts came from a group known as APT129, also known as “Cozy Bear,” that “almost certainly operate as part of Russian intelligence services.” The Canadian Communication Security Establishment, US Department for Homeland Security, the Cybersecurity Infrastructure Security Agency, and the National Security Agency shared the assessment, the NCSC said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

John Furey, Imvax CEO

A neu­ro­sur­geon spent the past 30 years de­vel­op­ing a neoanti­gen tu­mor vac­cine. Now he has $112M for a piv­otal test

As a neurosurgeon, David Andrews knew there wasn’t much he could do for his glioma patients after resecting — rarely fully — their tumor. Even with the best treatment and care available, median overall survival is just somewhere between 14 and 16 months.

Then in the 1990s, his mentor at Thomas Jefferson University introduced him to Renato Baserga, a pathologist who had been studying the effect of using antisense oligonucleotide to knock out the insulin-like growth factor type 1 receptor in cancers. As IGF-R1 drives tumor growth and metastasis, the preclinical reasoning went, implanting a molecule targeting the receptor together with the tumor material near lymph nodes can slow down the spread of the cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 85,300+ biopharma pros reading Endpoints daily — and it's free.

Full Bril­in­ta study re­sults show the blood thin­ner re­duces rate of sec­ondary stroke

AstraZeneca once projected its Brilinta drug to peak at $3.5 billion in sales, and though the blood thinner never reached that lofty goal, it received the latest positive signs in a string of recent good news.

The pharma released full details from its THALES study Thursday morning, which measured the effects of Brilinta and aspirin against aspirin alone in treating patients who had an acute ischemic stroke or transient ischemic attack. When taken twice daily with once-a-day aspirin for 30 days, the Brilinta combo reduced the risk of stroke and death by 17 percent, meeting the primary endpoint of the study.