Roche torch­es a moun­tain of biobucks, sweep­ing out a ros­ter of drugs in the lat­est pipeline cleanup

While Roche $RHH­BY post­ed its Q3 up­date on the num­bers, high­light­ing the im­por­tance of its new block­busters in re­plac­ing some ag­ing fran­chis­es, the R&D group used the oc­ca­sion to un­cer­e­mo­ni­ous­ly sweep out a ros­ter of losers from the pipeline.

At the top of the list, Roche is drop­ping a Phase III pro­gram for Actem­ra as a treat­ment for sys­temic scle­ro­sis. The move comes af­ter re­searchers con­clud­ed last fall that the drug “is as­so­ci­at­ed with ben­e­fits for skin fi­bro­sis, lung fi­bro­sis and phys­i­cal func­tion in pa­tients with SSc but in­creased the risk for se­ri­ous in­fec­tions.”

Re­moved from their Phase II pipeline with­out ex­pla­na­tion: RG6125, a Cad­herin-11 mAb for rheuma­toid arthri­tis.

The phar­ma play­er was an­gling for the big sec­ond-line ther­a­py group for RA, for pa­tients who fail on methotrex­ate and an an­ti-TNF-al­pha drug. RG6125 was billed as the first an­ti­body that tar­get­ed stro­mal cells, of­fer­ing a shot at treat­ing the dis­ease with­out sup­press­ing the im­mune sys­tem — some­thing that has se­vere phys­i­cal con­se­quences for pa­tients.

The drug start­ed the Phase II about a year ago, and ev­i­dent­ly has not per­formed well.

Six Phase I pro­grams didn’t make it to the next lev­el.

On the scrap heap this quar­ter (on page 49 of the re­view) you’ll find an an­ti­body di­rect­ed against the ty­ro­sine ki­nase re­cep­tor colony stim­u­lat­ing fac­tor 1 re­cep­tor that Roche had been de­vel­op­ing in com­bi­na­tion pack­ages for sol­id tu­mors, a Nav 1.7 pain drug part­nered with Xenon, an­oth­er sol­id tu­mor pro­gram from Ar­ray, an asth­ma drug and a fi­bro­sis ther­a­py.

At the top of this list is RG7155, or emac­tuzum­ab, an an­ti­body de­signed to block in­flam­ma­tion by in­hibit­ing the bind­ing of colony-stim­u­lat­ing fac­tor-1 (CSF-1) to CSF1R.

There were two com­bos that didn’t make it out of ear­ly-stage test­ing:

  • RG7155 emac­tuzum­ab + Tecen­triq for sol­id tu­mors
  • RG7155 emac­tuzum­ab + seli­cre­lum­ab

The next drug works to stop DNA re­pair mech­a­nisms, fa­cil­i­tat­ing the death of can­cer cells, much like PARP. In this case it’s a check­point ki­nase 1 in­hibitor, tar­get­ing a key en­zyme in as­sist­ing chemo.

  • RG7741 (GDC-0575) Chk1 inh – sol­id tu­mors

Way back in 2011 Genen­tech re­port­ed­ly paid $28 mil­lion up­front to pick up the drug from Ar­ray. And the pact re­port­ed­ly in­clud­ed some big mile­stones for the pre­clin­i­cal drug, even though Roche had an­oth­er Chk1 — GDC-0425 (RG7602) — in the pipeline.

I asked Roche about these drugs and they replied:

Emac­tuzum­ab showed promis­ing bi­o­log­i­cal ac­tiv­i­ty in a phase I study in sol­id tu­mours, as both a monother­a­py and in com­bi­na­tion with oth­er ther­a­pies. It was then in­ves­ti­gat­ed in ad­di­tion­al phase I/II stud­ies, in­clud­ing in com­bi­na­tion with Tecen­triq in pa­tients with ad­vanced sol­id tu­mours. Re­sults from this com­bi­na­tion tri­al in­di­cat­ed the com­bi­na­tion is not mean­ing­ful­ly bet­ter than Tecen­triq alone in this pa­tient pop­u­la­tion. As such, we are halt­ing the de­vel­op­ment pro­gram for emac­tuzum­ab. In Aug 2018 the de­ci­sion was made to dis­con­tin­ue futher de­vel­op­ment of emac­tuzum­ab.

As part of our com­mit­ment to fol­low the sci­ence, we al­so ex­plored emac­tuzum­ab as a treat­ment for oth­er in­di­ca­tions in­clud­ing pig­ment­ed vil­lon­odu­lar syn­ovi­tis (PVNS), a rare joint dis­ease that is caused by over­ex­pres­sion of CSF-1. While these in­di­ca­tions are not aligned with our core busi­ness, we want to en­sure pa­tients may one day be able to ben­e­fit from emac­tuzum­ab and will con­sid­er out-li­cens­ing op­por­tu­ni­ties as ap­pro­pri­ate.

As for RG6125 and RG7741: They “did not show the clin­i­cal ben­e­fit we ex­pect­ed and they were dis­con­tin­ued due to port­fo­lio pri­or­i­ti­za­tion.”

Next up: A pain deal gone bad. RG6029 (Genen­tech’s GDC-0310) Nav 1.7 in­hibitor for pain, which was be­ing de­vel­oped un­der a 7-year-old, $646 mil­lion deal with Xenon $XENE, is out the back door.  

Then there is RG7990 – a bis­pe­cif­ic from NovIm­mune tar­get­ing IL13/IL17 for asth­ma.

And fi­nal­ly we have a drug they marked as out-li­censed:

  • RG6069, an an­ti-fi­brot­ic agent.

Fail­ure, of course, is all part of R&D. Un­for­tu­nate­ly, de­vel­op­ers like Roche don’t like to pro­vide de­tails about what went wrong for its clin­i­cal drugs that flunk out.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.

Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.

Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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'We kept at it': Jef­frey Blue­stone plots late-stage come­back af­ter teplizum­ab shown to de­lay type 1 di­a­betes

Late-stage da­ta pre­sent­ed at the Amer­i­can Di­a­betes As­so­ci­a­tion an­nu­al meet­ing in 2010 pushed Eli Lil­ly to put a crimp on teplizum­ab as the phar­ma gi­ant found it un­able to re­set the clock on new­ly di­ag­nosed type 1 di­a­betes. At the same con­fer­ence but in dif­fer­ent hands nine years lat­er, the drug is mak­ing a crit­i­cal come­back by scor­ing suc­cess in an­oth­er niche: de­lay­ing the on­set of the dis­ease.

In a Phase II tri­al with 76 high-risk in­di­vid­u­als — rel­a­tives of pa­tients with type 1 di­a­betes who have di­a­betes-re­lat­ed au­toan­ti­bod­ies in their bod­ies — teplizum­ab al­most dou­bled the me­di­an time of di­ag­no­sis com­pared to place­bo (48.4 months ver­sus 24.4 months). The haz­ard ra­tio for di­ag­no­sis was 0.41 (p=0.006).

Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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