Gilead, Merck put aside rivalry to challenge GlaxoSmithKline for long acting HIV meds

Jason Mast

Editor

Joan But­ter­ton

Joan But­ter­ton was sit­ting 30,000 feet above the At­lantic, fly­ing to a con­fer­ence in Eu­rope, when the Mer­ck sci­en­tist seat­ed next to her start­ed gush­ing about the HIV mol­e­cule the big phar­ma had just li­censed from a small Japan­ese com­pa­ny. It was so po­tent in mon­keys, the sci­en­tist said, that they couldn’t fig­ure out what the low­est ef­fec­tive dose was and it stayed in the an­i­mals for an in­cred­i­bly long time, far longer than the ap­proved drugs HIV pa­tients took dai­ly.

Nine years and a few clin­i­cal tri­als lat­er, Mer­ck has shown that the drug, is­la­travir, can keep pa­tients’ virus­es sup­pressed with just one pill. Now But­ter­ton, who now runs Mer­ck’s late-stage in­fec­tious dis­ease tri­als, will try to chart a block­buster fu­ture for the drug, as the NJ phar­ma teams with a long­time ri­val to make it the base of a fran­chise that re­makes HIV treat­ment.

In a rare col­lab­o­ra­tion be­tween two of the biggest HIV drug de­vel­op­ers, Mer­ck and Gilead an­nounced Mon­day that they will col­lab­o­rate to turn one of the most promis­ing mol­e­cules from each of their pipelines in­to a two-drug com­bo that can pro­vide pa­tients op­tions out­side of the dai­ly pills that have dom­i­nat­ed the field for years.

“Re­al­ly, we’re see­ing this drug as some­thing that is foun­da­tion­al,” But­ter­ton told End­points News.

With the deal, Mer­ck and Gilead will com­bine two mol­e­cules with dif­fer­ent mech­a­nisms that have al­ready shown ef­fi­ca­cy in the clin­ic. Mer­ck’s is­la­travir is a new kind of re­verse tran­scrip­tase in­hibitor, sin­gle­hand­ed­ly muck­ing up two dif­fer­ent process­es the virus re­lies on to repli­cate. Gilead’s lenaca­pavir, which they re­cent­ly showed could ef­fec­tive­ly re­duce vi­ral lev­els in pa­tients with drug-re­sis­tant HIV,  in­hibits the HIV’s shell, com­mon­ly called its cap­sid.

The idea is that the com­bo could be­come a po­tent once-a-week pill and, in an­oth­er for­mu­la­tion, an in­jectable that pa­tients can take as in­fre­quent­ly as once every six months. Ei­ther of those ac­com­plish­ments would in­stant­ly make the drug a lead­ing con­tender in one of the com­pet­i­tive fields in HIV: the hunt for a long-act­ing drug.

It’s an im­por­tant branch of med­i­cine, po­ten­tial­ly help­ing pa­tients who strug­gle with or face stig­ma tak­ing a dai­ly pill. And it’s cur­rent­ly led by Glax­o­SmithK­line’s spin­out Vi­iV, which won ap­proval this year for a first-of-its-kind once-a-month shot for HIV pa­tients.

Mer­ck and Gilead are al­ready gam­ing out the po­ten­tial for a block­buster lay­ing out terms for how prof­it shar­ing will change if an­nu­al sales ex­ceed $2 bil­lion or $3.5 bil­lion, de­pend­ing on whether it’s the oral or in­jectable form.

Di­ana Brainard

In an in­ter­view, Gilead HIV chief Di­ana Brainard called the col­lab­o­ra­tion “his­toric,” tout­ing the po­ten­tial for the cock­tail to give new op­tions for pa­tients with HIV.

“They’re both high­ly po­tent,” Brainard said of the two mol­e­cules. “The more po­tent the drug is, the low­er the dose is and when you’re look­ing at long-act­ing, that’s im­por­tant be­cause you have to give a whole weeks of a dose, or whole three months worse of a dose in one oral pill or one in­jec­tion.”

An­a­lysts praised the deal for both teams. Piper San­dler’s Tyler Van Bu­ren said it was a “di­rect ac­knowl­edg­ment” from Gilead that af­ter years of a one-sided race be­tween the two drug­mak­ers, Mer­ck fi­nal­ly has a mol­e­cule that can com­pete. Jef­feries’ Michael Yee said it was an “in­cre­men­tal pos­i­tive” for Gilead that would al­low them to take a larg­er share of the mar­ket in the long term.

The two com­pa­nies will now com­bine the new drugs in mul­ti­ple tri­als, test­ing both pills and in­jectable forms. The first study will test an oral com­bo and be­gin in the sec­ond half of this year. Be­cause Gilead and Mer­ck have yet to de­vise a for­mu­la that com­bines the mol­e­cules in­to a sin­gle pill, the first vol­un­teers will sim­ply take one of each.

The com­pa­nies al­so have work to do on cre­at­ing a sin­gle in­jectable for­mu­la­tion, Brainard said, a com­pli­cat­ed task that could de­ter­mine how long the shot will last. They hope to have one for­mu­la­tion com­plete next year.

Gilead and Mer­ck will split costs 60/40. They will share prof­its 50/50 un­less sales ex­ceed $2 bil­lion per year for the oral for­mu­la or $3.5 bil­lion for the in­jectable for­mu­la. At that point, Gilead would be­gin tak­ing 65% of sales. Both com­pa­nies have an­oth­er type of mol­e­cule, an in­te­grase in­hibitor, in tri­als. In the deal, Mer­ck gave Gilead an op­tion to li­cense their in­te­grase in­hibitor and vice ver­sa.

The long-act­ing treat­ment pro­gram rep­re­sents just one of sev­er­al ap­pli­ca­tions each de­vel­op­er has for their mol­e­cules, along­side use in drug-re­sis­tant pa­tients and as pre-ex­po­sure pro­phy­lax­is to pre­vent in­fec­tion.  Mer­ck thinks an im­plant of is­la­travir alone could pro­tect pa­tients from an HIV for a year — an ap­pli­ca­tion that’s still in ear­ly de­vel­op­ment but which would pro­vide the clos­est thing the field has to a vac­cine.

“At Mer­ck, we are res­olute in our com­mit­ment to ad­vanc­ing the care of peo­ple liv­ing with HIV as part of our mis­sion to save and im­prove lives,” Mer­ck CEO Ken Fra­zier said in a state­ment. “This col­lab­o­ra­tion with Gilead brings to­geth­er two com­pa­nies ded­i­cat­ed to the fight against HIV to de­vel­op po­ten­tial new long-act­ing treat­ment op­tions, and is an im­por­tant step for­ward in our strat­e­gy to har­ness the full po­ten­tial of is­la­travir for the treat­ment of HIV.”