CRI re­port tracks ex­plo­sive growth of cell ther­a­pies in the glob­al pipeline, as Chi­na re­searchers mus­cle to­ward the front

The Can­cer Re­search In­sti­tute is shin­ing a light on the ex­plo­sive growth of cell ther­a­pies in the clin­ic, spot­light­ing Chi­na’s vir­tu­al overnight suc­cess in grab­bing a lead role in the field. And they’re ask­ing the world’s can­cer drug de­vel­op­ment com­pa­nies to adopt a new ap­proach that will help the in­dus­try man­age a fi­nite num­ber of po­ten­tial tri­al pa­tients while point­ing re­searchers to the most like­ly av­enue for do­ing some­thing im­por­tant — rather than just frit­ter­ing away bad­ly need­ed re­sources.

The non­prof­it CRI re­cent­ly quan­ti­fied the pro­lif­er­a­tion of I/O agents in the clin­ic, cap­tur­ing our at­ten­tion with the news that 164 PD-1/L1 ther­a­pies were in the pipeline, look­ing to whit­tle away at the block­buster lead­ers from Mer­ck and Bris­tol-My­ers Squibb. Now we learn from an up­date in Na­ture Re­views Drug Dis­cov­ery — penned by a team that in­cludes Jill O’Don­nell‐Tormey and Aiman Sha­l­abi — that they tracked down 753 cell ther­a­pies, with 375 in the clin­ic.

That fig­ure is up 87% in just 6 months, with 350 added to the pipeline around the world.

The tal­ly re­veals that “378 are in pre­clin­i­cal phase, 160 in phase I, 205 in phase II, 6 in phase II and 4 ap­proved (2 in the US, 1 in South Ko­rea and 1 in Italy),” re­ports the CRI. “In­ter­est­ing­ly, 404 of the 753 agents are chimeric anti­gen re­cep­tor (CAR) T cell ther­a­pies.”

Not sur­pris­ing­ly, the US is in the clear lead here, with 344 pro­grams. But Chi­na is num­ber two, and catch­ing up fast, with 203. In a field where aca­d­e­m­ic cen­ters fre­quent­ly play a lead role in demon­strat­ing their po­ten­tial, 125 of Chi­na’s pro­grams — 62% — are in the hands of aca­d­e­mics.

Here’s a look at the glob­al play­ing field:

In the mean­time, it’s get­ting rapid­ly eas­i­er to get these ther­a­pies pro­duced for clin­i­cal tri­als vir­tu­al­ly any­where. “(W)ith the rapid ad­vance­ment of lo­cal cell pro­duc­tion tech­nolo­gies, such as Clin­i­MACS Prodi­gy (Mil­tenyi Biotec), Co­coon (Lon­za) and Bea­con (Berke­ley Lights), we an­tic­i­pate a low en­try hur­dle for lo­cal man­u­fac­ture of cells for in­ves­ti­ga­tion­al clin­i­cal use.”

There are 113 tar­gets on the radar in this field, with 73 in the clin­ic. CD19 rules the roost, for now, with BC­MA a grow­ing but still rel­a­tive­ly small seg­ment. Here’s a look at the top 30:

The boom­ing on­col­o­gy re­search field has de­liv­ered some im­por­tant gains in the last two years. But at this rate, the gold rush for ad­vanc­ing new drugs is spurring the CRI to out­line some bad­ly need­ed re­forms. Here are three:

  • They’re ask­ing the R&D ex­ecs here to shift more of their fo­cus to in­tro­duc­ing ge­net­ic con­structs in­to cells, rather than con­cen­trate on vi­ral vec­tors, where a pro­duc­tion bot­tle­neck has de­vel­oped.
  • Rather than squan­der the lim­it­ed ac­cess to pa­tient vol­un­teers on a mas­sive num­ber of new stud­ies, they want de­vel­op­ers to move to adap­tive tri­al de­signs that ac­com­mo­date mul­ti­ple drugs and tar­gets at once.
  • And with the big push on to ex­pand in­to sol­id tu­mors, CRI wants de­vel­op­ers to fo­cus on the most im­por­tant tar­gets not cur­rent­ly be­ing treat­ed well with ex­ist­ing drugs.

There’s no R&D czar in the world, though, that can de­mand dis­ci­pline in this field. Large play­ers have been re­sis­tant to be­ing told what to do as much as the small­er play­ers. And every­one wants to con­trol their own eco­nom­ics. The mar­ket is dri­ving the growth of the field, but it can’t triage how it grows — un­less in­vestors start hold­ing back funds in search of more com­mon sense.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes more than a week af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Alex­ion wins pri­or­i­ty re­view for Ul­tomiris' aHUS in­di­ca­tion; FDA ex­pands ap­proval of Ver­tex's Symdeko

→ Alex­ion $ALXN has scored a speedy re­view for Ul­tomiris for pa­tients with atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) af­ter post­ing pos­i­tive da­ta from a piv­otal study in Jan­u­ary. The drug is the rare dis­ease com­pa­ny’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks. The de­ci­sion date has been set to Oc­to­ber 19. Late last year, Ul­tomiris se­cured ap­proval for noc­tur­nal he­mo­glo­bin­uria (PNH) pa­tients.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.

Ab­b­Vie gets a green light to re­sume re­cruit­ing pa­tients for one myelo­ma study — but Ven­clex­ta re­mains un­der a cloud

Three months af­ter reg­u­la­tors at the FDA forced Ab­b­Vie to halt en­rolling pa­tients in its tri­als of a com­bi­na­tion us­ing Ven­clex­ta (vene­to­clax) to treat drug-re­sis­tant cas­es of mul­ti­ple myelo­ma, the agency has green-light­ed the re­sump­tion of one of those stud­ies, while keep­ing the rest on the side­lines.

The CANO­VA (M13-494) study can now get back in busi­ness re­cruit­ing pa­tients to test the drug for a pop­u­la­tion that shares a par­tic­u­lar ge­net­ic bio­mark­er. To get that per­mis­sion, Ab­b­Vie — which is part­nered with Roche on this pro­gram — was forced to re­vise the pro­to­col, mak­ing un­spec­i­fied changes in­volv­ing risk mit­i­ga­tion mea­sures, pro­to­col-spec­i­fied guide­lines and an up­dat­ed fu­til­i­ty cri­te­ria.