Ver­tex and CRISPR Ther­a­peu­tics un­veil more pos­i­tive gene ther­a­py da­ta, but busul­fan again casts a shad­ow over the field

Less than 12 hours af­ter re­veal­ing a flop on its sec­ond shot for al­pha-1 an­tit­rypsin de­fi­cien­cy, Ver­tex plowed ahead with an­oth­er da­ta drop from its part­ner­ship with CRISPR Ther­a­peu­tics. And though the topline proved pos­i­tive, con­cerns over con­di­tion­ing agents con­tin­ue to linger over the col­lab­o­ra­tion, as well as the en­tire gene ther­a­py space.

Pre­sent­ing da­ta from two tri­als at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion an­nu­al meet­ing, the pair an­nounced that fol­low-up da­ta of at least three months for 22 pa­tients with ge­net­ic blood dis­or­ders in­di­cat­ed a “con­sis­tent and sus­tained” re­sponse to the ex­per­i­men­tal drug CTX001. All 15 pa­tients with trans­fu­sion-de­pen­dent be­ta tha­lassemia did not need fur­ther blood trans­fu­sions and all sev­en with se­vere sick­le cell dis­ease were pain free, the biotechs an­nounced.

There was one pa­tient not in­clud­ed in the da­ta cut­off of March 30, how­ev­er, who ex­pe­ri­enced a cere­bel­lar he­m­or­rhage less than three months af­ter be­ing treat­ed. The se­ri­ous side ef­fect was re­lat­ed to the busul­fan con­di­tion­ing gene ther­a­py pa­tients un­der­go be­fore re­ceiv­ing treat­ment, Ver­tex said, and has since re­solved.

Busul­fan has long proved tricky for com­pa­nies de­vel­op­ing gene ther­a­pies, with the chemo reg­i­men prov­ing a nec­es­sary but in­ten­sive process for pa­tients. It’s been linked in the past to can­cer and some have linked it to po­ten­tial cas­es of leukemia and myelodys­plas­tic syn­drome seen in blue­bird bio’s gene ther­a­py stud­ies.

Ad­di­tion­al­ly, as Ver­tex and CRISPR had pre­vi­ous­ly re­vealed, one be­ta tha­lassemia pa­tient ex­pe­ri­enced four se­ri­ous side ef­fects re­lat­ed or pos­si­bly re­lat­ed to CTX001. They all oc­curred with­in the con­text of an in­flam­ma­to­ry re­sponse and have al­so re­solved.

In the be­ta tha­lassemia study, in­ves­ti­ga­tors fol­lowed the 15 pa­tients for a range of four to 26 months, and the sick­le cell pa­tients from five to 22 months. Sev­en from across both stud­ies are more than a year out since re­ceiv­ing treat­ment. Fri­day’s re­sults are an up­date to a da­ta cut from De­cem­ber’s ASH con­fer­ence, which had on­ly in­clud­ed 10 pa­tients.

The gene ther­a­py in ques­tion, be­ing de­vel­oped joint­ly by Ver­tex and CRISPR, is an au­tol­o­gous ex vi­vo CRISPR/Cas9 treat­ment. Ver­tex teamed up with CRISPR back in 2015, but the pair ex­pand­ed on their part­ner­ship in April in a bid to de­vel­op the treat­ment more quick­ly.

In the ex­pan­sion, Ver­tex paid an ad­di­tion­al $900 mil­lion cash to take an­oth­er 10% of fu­ture sales from the gene edit­ing ther­a­py, with CRISPR hand­ing over re­spon­si­bil­i­ty for com­mer­cial­iz­ing CTX001 in the US. Along with oth­er re­cent changes to their part­ner­ship, the move ef­fec­tive­ly hands Ver­tex re­spon­si­bil­i­ty for man­u­fac­tur­ing the ther­a­py and stew­ard­ing it past reg­u­la­tors across the globe.

Should CTX001 be­come the first CRISPR-based ther­a­py to hit the mar­ket, that wa­ger would give Ver­tex a sig­nif­i­cant sales ad­van­tage over ri­vals like blue­bird. The Nick Leschly-run com­pa­ny has faced an up­hill climb for its gene ther­a­py pro­grams, ul­ti­mate­ly split­ting it­self in­to two com­pa­nies at the be­gin­ning of the year.

Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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Goldfinch Bio CEO Tony Johnson (L) and Karuna Therapeutics CEO Bill Meury

Karuna li­cens­es Goldfinch as­sets to com­pete with Boehringer In­gel­heim in neu­ro­science

Karuna Therapeutics is looking to compete with Boehringer Ingelheim on depression and anxiety with a new license to Goldfinch Bio’s assets, starting with $15 million to the shuttered biotech.

Karuna steps into an arena already being tested by Boehringer in multiple Phase II studies — the two are targeting transient receptor potential canonical 4 and 5, or TRPC4/5, which is thought to have a role in neuroscience indications. Goldfinch’s asset went through a Phase II in kidney diseases, but Karuna’s sights are set on mood and anxiety disorders for now.

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Roche's headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

Roche ditch­es fi­nal PhI­II for can­cer hope­ful, re­ports set­back for key drug in $1.4B buy­out

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials.

Now, the last piece of the program is gone.

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Simba Gill, Evelo Biosciences CEO

Sim­ba Gill stay­ing on at Evelo to weath­er lay­offs and a PhII fail

Simba Gill will be staying put as CEO of Evelo Biosciences for now.

Gill announced last year that he would be leaving the head position at Evelo to take on the role of executive partner at Flagship Pioneering. He was aiming to stay on until a successor was selected, but there’s a new course of action in the wake of a Phase II miss and a reduced headcount.

“I want to emphasize that I remain personally committed to Evelo and staying on to lead the organization. I continue to believe that Evelo is a remarkable opportunity in terms of the science, the platform, the type of products that we’re able to produce, and most importantly, the potential of millions of patients suffering from all stages of inflammatory disease,” Gill said on a conference call.

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