Blue­bird, Cel­gene add a promis­ing chap­ter to their suc­cess sto­ry with BC­MA-tar­get­ing CAR-T — and turn it around with in­vestors

CHICA­GO — Right now at Cel­gene $CELG and blue­bird $BLUE, it’s all about the Kar­M­Ma — and they’re look­ing to bur­nish theirs at AS­CO.

Nick Leschly

In a peek at the first batch of high­ly promis­ing da­ta to hit at AS­CO, in­ves­ti­ga­tors are am­pli­fy­ing ev­i­dence of pos­i­tive ob­jec­tive re­sponse rates for the drug, with an en­cour­ag­ing pro­gres­sion-free sur­vival rate of close to a year to il­lus­trate its po­ten­tial dura­bil­i­ty for pa­tients with far ad­vanced cas­es of mul­ti­ple myelo­ma — par­tic­u­lar­ly in the high-dose group. And it all looks tai­lor made for pri­or­i­ty han­dling at the FDA.

Ex­pec­ta­tions for this drug, though, have been pumped sky high — which might ex­plain why blue­bird’s stock slid deep­er in pre-mar­ket trad­ing Mon­day, down about 7%. Stalling myelo­ma by about a year may well be em­braced by the FDA, but with­out cur­ing cas­es a sig­nif­i­cant group of ob­servers came away ear­ly on dis­ap­point­ed by the drug’s prospects. Sev­er­al an­a­lysts, in­clud­ing Bri­an Sko­r­ney, came back with a sol­id score on the da­ta, and by Mon­day af­ter­noon the stock price had bounced back in­to the green.

The up­date keeps Cel­gene’s on­go­ing piv­otal study of the BC­MA-tar­get­ing bb2121 — Kar­M­Ma — square­ly in the CAR-T spot­light as one of the next big pro­grams to watch. Equipped with both break­through and PRIME des­ig­na­tions in the US and Eu­rope, reg­u­la­tors will like­ly be ready to whisk it through to the mar­ket with pos­i­tive da­ta. And re­searchers are mak­ing the case that their lead­ing BC­MA ef­fort has the legs to be a first-in-class con­tender for the ini­tial wave of BC­MA CAR-Ts.

Do­ing that re­quires ev­i­dence of dura­bil­i­ty, a re­li­able dose re­sponse and a clear safe­ty pro­file that won’t stall or kill their ther­a­py dur­ing the last stretch of this race.

“The dan­ger with some ear­ly pre­sen­ta­tions of the da­ta is, are they go­ing to be re­flec­tive when you get more pa­tients and more time,” says CEO Nick Leschly.  And you can add more drug.


For 11 pa­tients with high BC­MA ex­pres­sion get­ting the 450 mil­lion cell dose, the strin­gent com­plete re­sponse/com­plete re­sponse rate was 54.5%, with very good par­tial re­spons­es of 27.3% and 9% in the par­tial re­sponse group — a 91% ORR. Among low ex­pressers, that fell to 37.5% for CRs while the VG­PRs swelled to 50% and par­tial re­spons­es hit 12.5% — for a 100% ORR. Among 22 pa­tients get­ting a 150 mil­lion-plus dose, the CR rate was 50% with 36.4% VG­PRs and 9.1% PRs — a 95.5% ORR.

The over­all ob­jec­tive re­sponse rate in the study at this point was 80.6%.

High­light­ing dura­bil­i­ty, the re­searchers are post­ing a me­di­an progress-free sur­vival rate of 11.8 months among 18 pa­tients who re­ceived an ac­tive dose of 150 mil­lion CAR-T cells-plus. That com­pares well with the 2.7 months reg­is­tered for pa­tients on the in­ef­fec­tive dose used in the study, set­ting a base­line to un­der­score the ef­fi­ca­cy. In 16 pa­tients who were MRD (min­i­mal resid­ual dis­ease) — neg­a­tive, or a deep­er lev­el of com­plete re­mis­sion, the mPFS was 17.7 months.

Ge­of­frey Porges hailed the re­sults, but not­ed that in­vestors could be left want­i­ng more on the up­side. He not­ed:

We pre­vi­ous­ly sug­gest­ed that me­di­an PFS would be reached at 12 months in this up­dat­ed dataset and there­fore see the re­sult as most­ly con­fir­ma­to­ry, al­though some in­vestors may be dis­ap­point­ed that PFS was not clos­er to ~15 months.

Late last year at ASH blue­bird post­ed a 94% over­all re­sponse rate for bb2121, with a jaw-drop­ping 56% com­plete re­sponse rate among a small group of 18 pa­tients in heav­i­ly pre­treat­ed ac­tive dose co­horts. Three of those 10 CRs, though, were un­con­firmed at the time of the pre­sen­ta­tion in At­lanta.

“What we’re see­ing here that there is a clear dose re­sponse,” says blue­bird R&D chief David David­son. “To see a me­di­an PFS of 11.8 months in this heav­i­ly pre­treat­ed pa­tient pop­u­la­tion is very en­cour­ag­ing.”

And now they plan to bake every­thing they’ve learned in­to Kar­M­Ma.

To be sure, there con­tin­ued to be plen­ty of ev­i­dence of tox­i­c­i­ty, with a high rate of cy­tokine re­lease syn­drome — more than 80% in the high­er dose ranges — to raise con­cerns. One in three pa­tients ex­pe­ri­enced trou­bling cas­es of neu­ro­tox­i­c­i­ty. But the key point for the in­ves­ti­ga­tors here is that there have been no treat­ment-re­lat­ed deaths; CRS cas­es are be­ing han­dled with­out the grade 5 events that can halt or even kill a CAR-T pro­gram like this, as Juno found out to their own re­gret.

As far as Leschly is con­cerned, there’s al­so every rea­son to be­lieve that the bb2121 team can now stay well ahead of its ri­vals at J&J and Leg­end. J&J has just nailed an FDA OK for its own Phase I/II study for BC­MA CAR-T LCAR-B38M (JNJ-68284528), and they will look to jump on the fast track to an ac­cel­er­at­ed OK.

That drug is “not in­flu­enc­ing us in any shape or form,” says Leschly, adding that “we’ve treat­ed very dif­fer­ent pa­tient pop­u­la­tions.” Blue­bird’s pa­tients have been through as many as 7 or 8 lines of ther­a­py, and they’re too far ahead now for any new ar­rivals to catch up.

 Says Leschly: “We’re off to the races.” And they don’t ex­pect to get passed by any new­com­ers.

“As you said, the re­sults are en­cour­ag­ing based on what’s cur­rent­ly avail­able to pa­tients in 4th line and be­yond,” says Leschly. “As long as we can con­tin­ue to de­liv­er these re­sults in Kar­M­Ma, we have a path to get to these pa­tients in 4th line.”

Im­age: Nick Leschly (YouTube)

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.