Aslan turns fo­cus to bil­iary tract can­cer as lead drug flops in PhII gas­tric can­cer study

About a year af­ter se­cur­ing the full rights to de­vel­op and com­mer­cial­ize var­l­i­tinib from Ar­ray Bio­Phar­ma $AR­RY, Aslan Phar­ma $AL­SN said the drug failed to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mors of pa­tients with gas­tric can­cer in a mid-stage study.

Carl Firth

The Sin­ga­pore-based com­pa­ny — which is run by for­mer BD chief for As­traZeneca Carl Firth and went pub­lic in an un­der­whelm­ing IPO last May — has es­sen­tial­ly aban­doned test­ing the ex­per­i­men­tal drug in pa­tients with gas­tric can­cer and will con­cen­trate on stud­ies in bil­iary tract can­cer and oth­er in­di­ca­tions, it said on Mon­day.

Orig­i­nal­ly de­vel­oped by Ar­ray, the drug is al­so known as ASLAN001 and is an oral, small mol­e­cule that in­hibits the ac­tiv­i­ty of epi­der­mal growth fac­tor re­cep­tors HER1, HER2 and HER4 — which are mu­tat­ed or over­ex­pressed in many tu­mors and typ­i­cal­ly cause un­con­trolled growth. Its mech­a­nism of ac­tion is sim­i­lar to that of Roche’s can­cer drug Her­ceptin, which tar­gets HER2.

In the study, var­l­i­tinib was be­ing test­ed as a first-line treat­ment in pa­tients with gas­tric can­cer in ad­di­tion to a stan­dard chemother­a­py reg­i­men. Af­ter 12 weeks of treat­ment, pa­tients giv­en the drug + chemother­a­py ex­pe­ri­enced an av­er­age tu­mor shrink­age of 22%, while those on chemother­a­py alone saw their tu­mors shrink by 12.5% — how­ev­er that dif­fer­ence was not deemed sta­tis­ti­cal­ly sig­nif­i­cant. Aslan’s shares were down 24% be­fore the bell.

In terms of safe­ty, 73.1% of pa­tients on the ex­per­i­men­tal drug reg­i­men ex­pe­ri­enced a grade 3 or high­er ad­verse event, ver­sus 88.5% of pa­tients on chemother­a­py alone, Aslan said.

Ac­cord­ing to clin­i­cal­tri­als.gov, about 50 pa­tients were en­rolled in the study, which, if pos­i­tive, was de­signed to evolve in­to a Phase III tri­al eval­u­at­ing the drug in hun­dreds of pa­tients.

Oth­er than di­et, to­bac­co use, gen­der (male) and age (60-80), gas­tric or stom­ach can­cer is al­so linked to in­fec­tion with H. py­lori bac­te­ria. Over time it can lead to pre­can­cer­ous changes to the in­ner lin­ing of the stom­ach, ac­cord­ing to the Amer­i­can Can­cer So­ci­ety (ACS), which es­ti­mates the num­ber of new cas­es of stom­ach can­cer have de­creased about 1.5% each year over the last decade in the Unit­ed States, al­though in the late 1930s, stom­ach can­cer was the lead­ing cause of can­cer death in the re­gion. In oth­er parts of the world, stom­ach can­cer is much more com­mon, par­tic­u­lar­ly in less de­vel­oped coun­tries, the ACS added.

Mark McHale

“First-line gas­tric can­cer is a very chal­leng­ing in­di­ca­tion to treat and the ma­jor­i­ty of pa­tients present with ad­vanced dis­ease at ini­tial di­ag­no­sis,” Aslan’s COO Mark McHale said in a state­ment. “To date, no tar­get­ed ther­a­pies have been ap­proved to treat gas­tric can­cer with low HER-fam­i­ly ex­pres­sion. Whilst we are dis­ap­point­ed by the study find­ings, we are en­cour­aged by the pos­i­tive safe­ty da­ta and re­main con­fi­dent that var­l­i­tinib’s po­tent pan-HER in­hi­bi­tion has the po­ten­tial to yield ben­e­fits in bil­iary tract can­cer where HER fam­i­ly ex­pres­sion is known to be high.”

Da­ta from a first-line bil­iary tract can­cer study will be pre­sent­ed at a med­ical con­fer­ence lat­er this week, while top-line da­ta from a piv­otal study in sec­ond-line bil­iary tract can­cer are ex­pect­ed in the sec­ond half of 2019, the com­pa­ny said.

“While the var­l­i­tinib clin­i­cal da­ta gen­er­at­ed to date…have demon­strat­ed some ac­tiv­i­ty, we con­tin­ue to want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib giv­en that bil­iary tract can­cer has his­tor­i­cal­ly been a dif­fi­cult space for drug de­vel­op­ment and the mech­a­nis­tic ad­van­tages of var­l­i­tinib be­ing a pan-HER in­hibitor re­main un­clear, giv­en the im­pli­ca­tions of tar­get­ing HER4 re­main poor­ly un­der­stood. Over­all, while we’re pos­i­tive on Aslan’s Asia fo­cused de­vel­op­ment strat­e­gy and the ex­pe­ri­ence of the man­age­ment team, we want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib in a cat­a­lyst-rich 2019,” Leerink an­a­lysts wrote in a note.

In 2017, Aslan re­port­ed that var­l­i­tinib in­duced a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mor size in pa­tients with breast can­cer in a Phase II tri­al, but the drug did not con­fer any im­prove­ments in pro­gres­sion-free sur­vival or over­all sur­vival.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

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