As gene edit­ing ex­plodes, a new re­port from Gold­man says Chi­nese groups are seiz­ing the lead on CRISPR and CAR-T stud­ies

Con­trary to what you might be­lieve, bio­phar­ma com­pa­nies in the US are not the lead­ers in clin­i­cal tri­als us­ing gene edit­ing tech. While a slate of US/Eu­ro­pean pi­o­neers have been lin­ing up their first hu­man tri­als, in­ves­ti­ga­tors in Chi­na are al­ready well ahead in test­ing CRISPR-edit­ed cells in hu­mans, ac­cord­ing to a deep dive on gene ther­a­pies from Gold­man Sachs an­a­lyst Salveen Richter.

“As of the end of Feb­ru­ary 2018,” Richter and her team re­port­ed, “there were nine reg­is­tered clin­i­cal stud­ies test­ing CRISPR-edit­ed cells to treat var­i­ous can­cers and HIV in­fec­tion in Chi­na, vs. on­ly one study in the U.S. All of the stud­ies were ini­ti­at­ed / spon­sored by top-tier pub­lic hos­pi­tals across Chi­na, and >80 pa­tients were re­port­ed as be­ing treat­ed by these in­ves­ti­ga­tion­al genome med­i­cines.”

Last year alone, Richter adds, the Na­tion­al Nat­ur­al Sci­ence Foun­da­tion of Chi­na pro­vid­ed fund­ing for more than 90 CRISPR projects — more than 270 over the last 4 years. With no reg­u­la­tions on these gene edit­ing projects, hos­pi­tals in Chi­na in par­tic­u­lar have been quick to ac­cel­er­ate their CRISPR work, a sit­u­a­tion that might change soon if Chi­na’s main drug agency steps in and ap­plies the brakes, as Gold­man ex­pects will hap­pen.

And Chi­nese in­ves­ti­ga­tors are al­ready ri­val­ing the US in the to­tal num­ber of CAR-T stud­ies that are be­ing done. As of Feb­ru­ary, Gold­man Sachs count­ed 153 CAR-T tri­als in Chi­na, com­pared to 164 in the US, 73 in Eu­rope and 56 in all of the rest of the world com­bined.

The one com­pa­ny fur­thest out in front is Leg­end Biotech­nol­o­gy, which J&J paid $350 mil­lion to part­ner with as it en­tered the glob­al race to de­vel­op new ther­a­pies in the wake of his­toric ap­provals for Kym­ri­ah (No­var­tis) and Yescar­ta (Gilead/Kite). And if these com­pa­nies and tri­als hit pay-dirt da­ta, as they promise to, Gold­man be­lieves that Chi­na will reap a con­sid­er­able ben­e­fit by sell­ing these ther­a­pies at a much low­er rate than the pi­o­neers on the mar­ket, spurring a sig­nif­i­cant amount of med­ical tourism.

What is this kind of mar­ket worth for the ri­vals look­ing to com­pete in it?

That de­pends on the sup­ply of pa­tients.

If your new genome med­i­cine ei­ther promis­es to cure a dis­ease or de­lay any fur­ther ther­a­py for a lengthy pe­ri­od of time, notes the Gold­man re­port, then your mar­ket could play out quick­ly as you race through the pa­tient pool that is avail­able. That’s what Gilead ex­pe­ri­enced when it came up with a pain­less cure for he­pati­tis C.

Not on­ly did the drugs from Gilead shrink the pool, Gold­man re­ports in a cold analy­sis of the num­bers, they al­so re­duced the num­ber of car­ri­ers present to keep spread­ing the dis­ease, fur­ther shrink­ing the mar­ket. From the re­port:

The po­ten­tial to de­liv­er “one shot cures” is one of the most at­trac­tive as­pects of gene ther­a­py, ge­net­i­cal­ly-en­gi­neered cell ther­a­py and gene edit­ing. How­ev­er, such treat­ments of­fer a very dif­fer­ent out­look with re­gard to re­cur­ring rev­enue ver­sus chron­ic ther­a­pies, par­tic­u­lar­ly in cer­tain dis­eases where it is pos­si­ble to cure a large pro­por­tion of the preva­lent pa­tient pool (or at least pre­vent an ad­di­tion­al dose from be­ing re­quired for an ex­tend­ed pe­ri­od). While this propo­si­tion car­ries tremen­dous val­ue for pa­tients and so­ci­ety, it could rep­re­sent a chal­lenge for genome med­i­cine de­vel­op­ers look­ing for sus­tained cash flow. Gilead is a case in point, where the suc­cess of its he­pati­tis C fran­chise has grad­u­al­ly ex­haust­ed the avail­able pool of treat­able pa­tients. 

The most lu­cra­tive dis­eases for these new cu­ra­tive ther­a­pies, Richter adds, would be big fields like he­mo­phil­ia or ar­eas where there’s a large sup­ply of new pa­tients each year — like can­cer. Spinal mus­cu­lar at­ro­phy, which af­flicts a stan­dard set of in­fants each year, is al­so vi­able. 

That may not be the kind of math that bio­phar­ma ex­ecs like to dis­cuss in pub­lic, but it’s cer­tain­ly the kind of equa­tions they re­view care­ful­ly while de­cid­ing how to spend R&D bud­gets.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.