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.

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Vas Narasimhan. Getty Images

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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

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HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

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Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

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Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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