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.

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.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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