Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

As J&J at­tempts to jos­tle past Bris­tol-My­ers Squibb and blue­bird for a land­mark ap­proval of its an­ti-BC­MA CAR-T — and while Glax­o­SmithK­line maps a quick path to the FDA rid­ing on its own BC­MA-tar­get­ing an­ti­body-drug con­ju­gates — the bis­pecifics are ar­riv­ing on the scene to stake a claim for a mar­ket that could cross $10 bil­lion per year.

The main ri­val­ry in mul­ti­ple myelo­ma is shap­ing up to be one be­tween Re­gen­eron and Bris­tol-My­ers, which picked up a bis­pe­cif­ic an­ti­body to BC­MA through its re­cent­ly closed $74 bil­lion takeover of Cel­gene. Both pre­sent­ed promis­ing first-in-hu­man da­ta at the ASH 2019 meet­ing.

Bri­an Sko­r­ney

“Al­though Cel­gene has both a time and myelo­ma ex­pe­ri­ence ad­van­tage, we be­lieve Re­gen­eron is close be­hind and could even catch up if the megamerg­er leads to some pro­gram de­lays” was Baird an­a­lyst Bri­an Sko­r­ney’s take as he scored the first myelo­ma da­ta for REGN5458.

With bis­pecifics the gen­er­al idea is to bridge T cells and tu­mors cells, there­by in­duc­ing the killing of can­cer. REGN5458, in par­tic­u­lar, binds to the CD3 re­cep­tor on the im­mune cells and BC­MA on mul­ti­ple myelo­ma cells.

In­ves­ti­ga­tors had da­ta on the first two dose groups to re­port from the on­go­ing Phase I/II dose es­ca­la­tion study, in which 3 pa­tients were giv­en 3mg week­ly dos­es and 4 pa­tients re­ceived 6mg. Over­all, 4 of them record­ed a re­sponse — giv­ing rise to a 57% re­sponse rate over­all — 3 of them from the 6mg group (75% re­sponse rate there). Among those three tak­ing the high­er dose, two passed the cru­cial test of be­ing min­i­mal resid­ual dis­ease (MRD) neg­a­tive, a high bar sug­gest­ing no can­cer cells were de­tectable in their bone mar­row.

Is­rael Lowy

No­tably, these pa­tients have had a me­di­an of sev­en lines of pri­or ther­a­py and had all failed CD38 an­ti­body treat­ment. And at the 6mg dose lev­el, the me­di­an num­ber of pri­or treat­ment was even high­er at 9.5, Sko­r­ney not­ed.

Cy­tokine re­lease syn­drome, ane­mia and lym­phope­nia were all doc­u­ment­ed, though Re­gen­eron said the ad­verse events were not dose lim­it­ing.

Their re­sults come on the heels of Bris­tol-My­ers/Cel­gene’s da­ta re­veal, in which CC-93269 showed an 89% re­sponse rate in the high­est dose of 10mg af­ter be­ing in­ves­ti­ga­tors went up from 0.15mg with 30 pa­tients to­tal.

“CC-93269 shows promis­ing dose-de­pen­dent ef­fi­ca­cy, in­clud­ing MRD-neg­a­tive sCRs, with a con­ve­nient ad­min­is­tra­tion sched­ule in pa­tients with heav­i­ly pre­treat­ed re­lapsed/re­frac­to­ry mul­ti­ple myelo­ma.”

Most of the grade 3 or high­er ad­verse events were neu­trope­nia, ane­mia and in­fec­tions, the in­ves­ti­ga­tors not­ed, though cy­tokine re­lease syn­drome al­so cropped up in 76% of all pa­tients in the tri­al.

In the Re­gen­eron tri­al, three pa­tients ex­pe­ri­enced CRS, amount­ing to a 42% oc­cur­rence.

“We are en­cour­aged to see promis­ing, rapid clin­i­cal ac­tiv­i­ty even at the ini­tial two dos­es of REGN5458 in heav­i­ly pre­treat­ed pa­tients with mul­ti­ple myelo­ma,” Is­rael Lowy, head of clin­i­cal and trans­la­tion­al sci­ences for on­col­o­gy at Re­gen­eron, said in a state­ment. “We are ac­tive­ly re­cruit­ing pa­tients in­to high­er dose groups in this tri­al and look for­ward to shar­ing fur­ther re­sults in 2020.”

Lowy added that the Tar­ry­town, NY-based biotech has ini­ti­at­ed a tri­al for its sec­ond BC­MA/CD3 bis­pe­cif­ic, which binds dif­fer­ent­ly. They are mov­ing fast — and they need to in a field brim­ming with com­peti­tors.

Pfiz­er is ad­vanc­ing its own ver­sion, al­though the ab­sence of equiv­a­lent­ly promis­ing da­ta at ASH pushed Sko­r­ney to sur­mise “not all bis­pecifics are cre­at­ed equal­ly.” Ab­b­Vie al­so got its hands on a bis­pe­cif­ic hook­ing to the same tar­gets from a $90 mil­lion deal with Teneo­bio.

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.

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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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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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.

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.

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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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.