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)

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

The End­points 11: They've got mad mon­ey and huge am­bi­tions. It's time to go big or go home

These days, selecting a group of private biotechs for the Endpoints 11 spotlight begins with a sprint to get ahead of IPOs and the M&A teams at Big Pharma. I’ve had a couple of faceplants earlier this year, watching some of the biotechs on my short list choose a quick leap onto Nasdaq or into the arms of a buyer.

Vividion, you would have been a great pick for the Endpoints 11. I’m sorry I missed you.

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Dave Lennon, former president of Novartis Gene Therapies

So what hap­pened with No­var­tis Gene Ther­a­pies? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

FDA au­tho­rizes Pfiz­er's vac­cine boost­er for se­niors, those at high risk for se­vere Covid-19

The Biden administration’s goal of kicking off its booster shot drive for the entire US population this week is not quite going as planned.

First, Pfizer applied for approval of a supplemental application for the booster shots, but since last Friday’s adcomm reviewing them, the plan has devolved into an EUA, which the FDA issued late Thursday evening.

The population that is now eligible for the booster, six months after receiving the first pair of Pfizer-BioNTech vaccines, also narrowed from what Pfizer applied for (everyone who’s eligible for the initial Pfizer shots) to just those who are 65 or older, or at high-risk of a Covid infection, including health care workers and others with occupational hazards.

Stéphane Bancel, AP Images

Fi­nal analy­sis of US-fund­ed Mod­er­na Covid vac­cine tri­al shows 98% ef­fi­ca­cy against se­vere dis­ease

A final look at the results of the placebo-controlled Moderna trial in the New England Journal of Medicine, published Thursday afternoon, shows how the vaccine continues to prevent Covid-19 and severe cases after more than five months following the second shot.

Of the more than 30,000 enrolled in the trial that ultimately led to the vaccine’s EUA, only two people in the vaccine group got a severe form of the disease, compared to 106 in the placebo group — leading to an efficacy of 98%.

Emma Walmsley, GlaxoSmithKline CEO (Credit: Fang Zhe/Xinhua/Alamy Live News)

The fire un­der Glax­o­SmithK­line's Em­ma Walm­s­ley grows as an­oth­er well-known ac­tivist in­vestor grabs its pitch­fork — re­port

Bluebell Capital Partners, a proxy brawler fresh off a campaign to oust global food giant Danone’s CEO and most of its board of directors, has bought a stake in UK drugmaker GlaxoSmithKline with its eyes trained directly on Emma Walmsley, the Financial Times reported Wednesday.

The London-based hedge fund joins another notorious activist firm in Paul Singer’s Elliott Management, which earlier this year called for a shakeup in leadership at GSK to handle what the company described as a wealth of riches across the drug giant’s portfolio hindered by limited vision from top staff.

FDA+ roundup: Bs­U­FA III ready for show­time, court tells FDA to re-work com­pound­ing plan, new guid­ance up­dates and more

The FDA has now spelled out what exactly will be included in the third iteration of Biosimilar User Fee Act (BsUFA) from 2023 through 2027, which similarly to the prescription drug deal, sets fees that industry has to pay for submitting applications, in exchange for firm timelines that the agency must meet.

This latest deal includes several sweeteners for the biosimilar industry, which has yet to make great strides in the US market, with shorter review timelines for safety labeling updates and updates to add or remove an indication that does not contain efficacy data.

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Joshua Liang, Clover Biopharmaceuticals CEO

With world still in sore need of dos­es, Clover says its Covid-19 vac­cine is 67% ef­fec­tive in Phase III

With concerns about the Delta variant rising and much of the world still in desperate need of vaccine doses, a Chinese biotech announced Wednesday that a new shot has shown positive results in a large trial against Covid-19, including new variants.

Clover Biopharmaceuticals announced Wednesday that its vaccine candidate showed 79% efficacy against the Delta variant in a Phase II/III trial dubbed Spectra, and 67% effective against Covid-19 overall.