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.

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.

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.