Will Ab­b­Vie bite? De­ci­sion time af­ter Abl­ynx's rheuma­toid arthri­tis drug fails a key study

Abl­ynx has come to the cross­roads with Ab­b­Vie on their block­buster deal to de­vel­op a new IL-6 drug for rheuma­toid arthri­tis. And the Bel­gian biotech com­pa­ny has some ex­plain­ing to do.

This morn­ing Abl­ynx re­leased an­oth­er messy set of Phase IIb da­ta on vo­bar­il­izum­ab. Com­bined with methotrex­ate, the com­bi­na­tion of vo­bar­il­izum­ab and methotrex­ate failed on the pri­ma­ry end­point, un­able to sig­nif­i­cant­ly dis­tin­guish it­self on most out­comes tied to the key mea­sure: An im­prove­ment of at least 20% on a dis­ease rat­ing score – ACR20 – af­ter 12 and 24 weeks of treat­ment. The drug even fell short on mea­sur­ing pa­tients’ abil­i­ty to func­tion bet­ter, with 71% in the methotrex­ate arm re­port­ing a clin­i­cal­ly mean­ing­ful im­prove­ment in phys­i­cal func­tion com­pared to 65% tak­ing a com­bi­na­tion of vo­bar­il­izum­ab and methotrex­ate.

The drug/methotrex­ate com­bo did bet­ter on ACR50 and ACR70 scores as well as scores for low dis­ease ac­tiv­i­ty. But in an in­tense­ly com­pet­i­tive field, Ab­b­Vie is fac­ing a Q4 dead­line to de­cide whether it will buy the drug and square off against far more ad­vanced ri­vals like Eli Lil­ly and In­cyte (baric­i­tinib), GSK and J&J (sirukum­ab) and Re­gen­eron/Sanofi (sar­ilum­ab). Ab­b­Vie al­so has its own Phase III ef­fort un­der­way, which it has high hopes for.

Shares of Abl­ynx {Eu­ronext Brus­sels: $ABLX} ini­tial­ly surged Tues­day, but slumped by mid-morn­ing, trad­ing down about 4%.

It can be hard to com­pare da­ta on these drugs. Abl­ynx chose to sim­ply se­lect pa­tients al­ready on methotrex­ate to com­pare their com­bo. The com­pe­ti­tion, though, has been rack­ing up late-stage suc­cess­es among treat­ment-re­sis­tant pa­tients or in head-to-head stud­ies with Ab­b­Vie’s Hu­mi­ra, the world’s biggest drug fran­chise at $14 bil­lion in 2015 rev­enue.

The lat­est da­ta set comes just one month af­ter Abl­ynx al­so demon­strat­ed that their drug was at best a matchup against Roche’s Actem­ra (ap­proved in 2010) on the key ACR scores, though it did bet­ter on dis­ease ac­tiv­i­ty scores.

Abl­ynx is paint­ing all of this as a sol­id suc­cess point­ing to “best-in-class po­ten­tial,” hop­ing to per­suade an­a­lysts to fo­cus in on the high scores or eas­i­er treat­ment reg­i­men for their drug and ig­nore what they’re call­ing a high place­bo re­sponse. Pay­ers, though, are like­ly to de­ter­mine that the drug proves that gener­ic methotrex­ate or an ex­ist­ing brand­ed drug is ei­ther as good or al­most as good as the ex­per­i­men­tal drug in com­bi­na­tion with methotrex­ate. And it will have a hard time catch­ing up with oth­er drugs that are much far­ther along in the pipeline.

Ab­b­Vie has to de­cide now whether it will take a chance on the drug, and take it in­to Phase III as oth­ers are look­ing for an ap­proval.

Ab­b­Vie paid $175 mil­lion up­front to part­ner with Abl­ynx on this drug, a big piece of an $840 mil­lion deal that gives Ab­b­Vie the op­tion to take it through Phase III. Ab­b­Vie, though, can be dis­tinct­ly un­sen­ti­men­tal about mar­gin­al drugs, as it proved with its de­ci­sion to bag its deal with In­fin­i­ty af­ter a suc­cess­ful, but com­mer­cial­ly un­con­vinc­ing, study of a lead can­cer drug.

Michael Sev­eri­no, Ex­ec­u­tive Vice Pres­i­dent, Chief Sci­en­tif­ic Of­fi­cer, Ab­b­Vie

There’s al­so a pre­ferred late-stage pro­gram at Ab­b­Vie to con­sid­er. Last fall, Ab­b­Vie axed a col­lab­o­ra­tion it has in place with Gala­pa­gos for their JAK1 in­hibitor fil­go­tinib (GLP0634), say­ing it pre­ferred to take their in-house pro­gram for ABT-494 in­to Phase III for arthri­tis.

“We be­lieve ABT-494 has the po­ten­tial to be­come a best-in-class ther­a­py, par­tic­u­lar­ly in the most chal­leng­ing pa­tient pop­u­la­tion of TNF-in­ad­e­quate re­spon­ders,” Ab­b­Vie CSO Michael Sev­eri­no not­ed af­ter the Phase II da­ta came out in Sep­tem­ber. The Phase III start­ed in Jan­u­ary.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

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Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

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