As­traZeneca’s $7B bet on Dai­ichi Sankyo’s an­ti­body drug con­ju­gate pays off with piv­otal da­ta to back their reg­u­la­to­ry pitch­es

Buoyed by the per­for­mance of its on­col­o­gy drugs, in March As­traZeneca chief Pas­cal So­ri­ot bet big to part­ner with Dai­ichi Sankyo on its ex­per­i­men­tal breast can­cer drug, with $1.35 bil­lion up­front in a deal worth up to rough­ly $7 bil­lion. On Wednes­day, the Japan­ese drug­mak­er said the ther­a­py had cleared a piv­otal mid-stage study, paving the way for reg­u­la­to­ry sub­mis­sions in the first half of fis­cal 2019.

The drug, trastuzum­ab derux­te­can, is an an­ti­body drug con­ju­gate (ADC) — ther­a­peu­tics in which a can­cer-killing tox­in is at­tached to a spe­cif­ic an­ti­body us­ing a biodegrad­able link­er — for can­cers that ex­press HER2, a pro­tein as­so­ci­at­ed with ag­gres­sive dis­ease that of­ten re­sides on cer­tain breast can­cer cells. About 30% of breast can­cers are HER2 pos­i­tive, ac­cord­ing to the NIH’s Na­tion­al Can­cer In­sti­tute. De­spite treat­ment with trastuzum­ab (Roche’s Her­ceptin), per­tuzum­ab (Roche’s Per­je­ta), and T-DM1 (Roche’s Kad­cy­la) — many breast can­cer pa­tients con­tin­ue to see their dis­ease progress, the com­pa­ny said.

In the phase II DES­TINY-Breast01 tri­al, trastuzum­ab derux­te­can was eval­u­at­ed in pa­tients with HER2-pos­i­tive un­re­sectable and/or metasta­t­ic breast can­cer, who dis­ease had pro­gressed de­spite Kad­cy­la ther­a­py.  The main goal of the 253-pa­tient study was ob­jec­tive re­sponse rate, while sec­ondary end­points in­clud­ed du­ra­tion of re­sponse, pro­gres­sion-free sur­vival and over­all sur­vival.

As as­sessed by an in­de­pen­dent re­view com­mit­tee, the re­sponse-rate in the heav­i­ly-pre­treat­ed glob­al pa­tient pop­u­la­tion mir­rored the “un­prece­dent­ed” clin­i­cal ac­tiv­i­ty in the re­cent­ly pub­lished phase I tri­al, in which a large pro­por­tion of pa­tients achieved dis­ease con­trol, and a long du­ra­tion of re­sponse, Dai­ichi said.

In this ear­ly-stage study, the first por­tion of the tri­al was ded­i­cat­ed to find­ing the op­ti­mal dose of the drug to use in the sec­ond tranche of the tri­al. From the evalu­able 111 pa­tients in the sec­ond phase of the tri­al — 66 achieved a con­firmed ob­jec­tive re­sponse; and 104 ex­pe­ri­enced con­firmed dis­ease con­trol, with a me­di­an fol­low-up of 9·9 months. The me­di­an du­ra­tion of re­sponse was 20·7 months, the me­di­an pro­gres­sion-free sur­vival was 22·1 months and tu­mour shrink­age was ob­served in 102 pa­tients with mea­sur­able le­sions who had at least one post­base­line scan. From a safe­ty and tol­er­a­bil­i­ty per­spec­tive, eval­u­at­ed pa­tients had one or more treat­ment-emer­gent ad­verse event of any grade.

An­toine Yver

De­tailed re­sults from the mid-stage study will be pre­sent­ed at an up­com­ing med­ical meet­ing.

“These re­sults con­firm our com­mit­ment to pur­sue ac­cel­er­at­ed reg­u­la­to­ry path­ways in HER2 pos­i­tive metasta­t­ic breast can­cer…” said An­toine Yver, glob­al head of on­col­o­gy R&D at Dai­ichi Sankyo, in a state­ment.

Trastuzum­ab derux­te­can, which has se­cured break­through ther­a­py sta­tus and fast track des­ig­na­tion from the FDA, is an HER2-tar­get­ed ADC with a topoi­so­merase I in­hibitor pay­load — a chemother­a­peu­tic agent de­signed to in­ter­rupt DNA repli­ca­tion in can­cer cells. It is be­ing de­vel­oped for oth­er HER2-ex­press­ing can­cers in­clud­ing gas­tric can­cer, with an added fo­cus on non-small cell lung and col­orec­tal can­cer.

If ap­proved, Dai­ichi will book drug sales in the Unit­ed States and cer­tain coun­tries in Eu­rope, in ad­di­tion to oth­er mar­kets where it has af­fil­i­ates — while As­traZeneca $AZN will book sales in all oth­er glob­al mar­kets, in­clud­ing Chi­na, Aus­tralia, Cana­da and Rus­sia.

So­ri­ot un­veiled the Dai­ichi tie-up months af­ter ex­e­cut­ing a re­struc­ture of its R&D by dis­man­tling the Med­Im­mune name and di­vid­ing de­vel­op­ment op­er­a­tions be­tween can­cer — un­der new ar­rival Jose Basel­ga — and every­thing else un­der Mene Pan­ga­los.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

'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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.