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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Sijmen de Vries, Pharming CEO

FDA ap­proves Pharm­ing drug for ul­tra-rare im­mun­od­e­fi­cien­cy dis­ease

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.