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.

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