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.

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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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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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 with any issues.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources.