Lat­est J&J-part­nered Leg­end Biotech da­ta spot­light con­tin­ued high re­sponse rate but 10 pa­tient deaths

Leg­end Biotech has has a good three years ever since the then-lit­tle known biotech un­veiled a round of BC­MA CAR-T da­ta at AS­CO. It helped net them a part­ner­ship with J&J and, more re­cent­ly, one of biotech his­to­ry’s biggest IPOs.

Now, the Nan­jing-based biotech un­veiled their largest set of da­ta for the ther­a­py, show­ing in­ter­im re­sults from a piv­otal US study con­duct­ed with J&J. The da­ta af­firmed the drug’s now well-doc­u­ment­ed ef­fi­ca­cy, with a 94% re­sponse rate and a 55% com­plete re­sponse rate, but it al­so re­vealed that, out of 97 pa­tients in the study, 10 died.

Eight of the deaths were from ad­verse events — whether re­lat­ed or un­re­lat­ed — and two were from dis­ease pro­gres­sion. No­tably, though, on­ly one death was from cy­tokine re­lease syn­drome, the in­flam­ma­to­ry con­di­tion that has dogged CAR-T since the first ex­per­i­men­tal ther­a­pies were put in­to hu­mans.

Leg­end dis­closed the CRS death, along with two oth­ers, in their S-1 this spring.

The com­pa­ny al­so not­ed a 20.6% rate of neu­ro­tox­i­c­i­ty, an­oth­er com­mon dan­ger­ous CAR-T side ef­fect. Af­ter the last cut of da­ta in 29 pa­tients in De­cem­ber, they had said “neu­ro­tox­i­c­i­ty was in­fre­quent­ly ob­served.”

Of course, se­vere side ef­fects have not al­ways held up CAR-T treat­ments in the past, par­tic­u­lar­ly when they al­so brought com­pelling ef­fi­ca­cy da­ta, and the J&J in­ves­ti­ga­tors said the da­ta were “con­sis­tent” with pri­or stud­ies. No­var­tis, for in­stance, saw 3 deaths in its piv­otal study for Kym­ri­ah and more than half of its pa­tients ex­pe­ri­ence neu­ro­log­i­cal symp­toms.

Safe­ty splits could be­come par­tic­u­lar­ly rel­e­vant, though, as J&J seeks to go head-to-head with the ri­val mul­ti­ple myelo­ma CAR-T treat­ment from blue­bird and Bris­tol My­ers Squibb, which is al­ready sit­ting be­fore the FDA.

In their most re­cent phase II da­ta, blue­bird sim­i­lar­ly saw one CRS-re­lat­ed death out of 140 pa­tients, but didn’t dis­close oth­er deaths in the tri­al. They re­port­ed that 3.1% of pa­tients had grade 3 or high­er neu­ro­tox­i­c­i­ties.

That da­ta set al­so showed re­duced ef­fi­ca­cy com­pared to what Leg­end showed in to­day’s cut, con­tin­u­ing a trend since AS­CO 2017. (Blue­bird main­tained at the time that Leg­end chose eas­i­er pa­tients). They saw an 81.5% re­sponse rate in the high­est per­form­ing dose group, with 35.2% see­ing some form of com­plete re­sponse.

J&J wasn’t yet able to col­lect du­ra­tion of re­sponse da­ta, but they showed that one pa­tient has re­spond­ed for around 20 months. Of pa­tients who were fol­lowed for 6 months, 87.4% had not seen their can­cers progress at that time and 93.8% were still alive.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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Roche amps up its bis­pe­cif­ic at­tack on Eylea with more PhI­II da­ta — but just how threat­en­ing is it?

Roche has another stack of data to back up its longer-acting challenger to Eylea — although it’s still far from certain just how much they can threaten Regeneron’s dominance.

The latest Phase III results come from two trials that enrolled 1,329 patients with neovascular age-related macular degeneration. With 45% of people in both studies getting faricimab 16 weeks apart during the first year, the bispecific still induced the same level of gains in visual acuity as Eylea every 8 weeks did, Roche’s Genentech reported.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.