Vertex shares take a hit as liver tox forces the research team to scrap a PhII drug for AAT patients — raising some big pipeline questions – Endpoints News

Ver­tex is tak­ing the ax to one of their rare dis­ease drugs af­ter ev­i­dence of liv­er dam­age emerged in a key Phase II study that blocks any us­es of the high­er dos­es that would be need­ed to treat ge­net­ic cas­es of al­pha-1 an­tit­rypsin de­fi­cien­cy.

The big biotech had high­light­ed a sim­i­lar ap­proach to mid-stage work that got them through ma­jor R&D work in cys­tic fi­bro­sis, which cre­at­ed the foun­da­tion the com­pa­ny is built on.

But in the tri­al of some 50 pa­tients, 4 tak­ing dif­fer­ent dos­es of the drug demon­strat­ed el­e­vat­ed liv­er en­zymes “greater than 8 times the up­per lim­it of nor­mal.”

Those cas­es re­solved, but there’s no get­ting around the safe­ty bar­ri­er now erect­ed against its use among these pa­tients. And the news took a painful 12% bite out of the com­pa­ny’s stock af­ter the bell on Wednes­day.

“Based on the liv­er en­zyme el­e­va­tions ob­served, along with the de­ter­mi­na­tion that we would not be able to safe­ly achieve tar­get­ed ex­po­sure lev­els with VX-814, we are dis­con­tin­u­ing fur­ther de­vel­op­ment of this mol­e­cule,” said Ver­tex CMO Car­men Boz­ic in a pre­pared state­ment.

For Ver­tex, the set­back could loom larg­er than any sin­gle pro­gram might nor­mal­ly war­rant. The com­pa­ny, now man­aged by a new CEO, has to prove to in­vestors that it can go past its big suc­cess with CF and prove it can de­vel­op drugs for oth­er con­di­tions. Some, like Ge­of­frey Porges, see to­day’s fail as an omi­nous sign.

In­vestors are like­ly to ques­tion whether the her­ald­ed Ver­tex re­search ca­pa­bil­i­ty is re­al­ly val­i­dat­ed be­yond CF, and there­fore what sort of val­ue the stock de­serves be­yond the present val­ue of the CF fran­chise alone. In our sum of the parts analy­sis, Ver­tex’s CF fran­chise alone is worth ~$220-240/share, and this is the range we ex­pect the stock to trade to af­ter this dis­clo­sure.

This doesn’t mark the end of the AAT pro­gram, though. Ver­tex has a “struc­tural­ly dis­tinct” drug dubbed VX-864 in Phase II with da­ta due out in 2021. And they have oth­er back­up mol­e­cules at the ready in case that pro­gram al­so ends in fail­ure.

Much of the fo­cus in this are­na has cen­tered on RNAi drugs from some of the big play­ers, which have been team­ing up on clin­i­cal ef­forts. Ar­row­head just signed up to part­ner with Take­da on AAT while Al­ny­lam and Dicer­na re­cent­ly joined forces as well. Ver­tex had one of the al­ter­na­tive ef­forts in place.