Gilead CSO Nor­bert Bischof­berg­er

Four years af­ter Gilead ac­quired mo­melo­tinib in its $510 mil­lion buy­out of YM Bio­Sciences, the big — and what ap­pears to be in­creas­ing­ly un­lucky — biotech was forced to re­port that the drug per­formed poor­ly in its two Phase III myelofi­bro­sis tri­als. And the fourth straight pipeline flop quick­ly spurred fresh spec­u­la­tion that Gilead will soon have to tap in­to its big cash re­serves for a ma­jor ac­qui­si­tion.

The JAK in­hibitor scored on a non-in­fe­ri­or­i­ty show­down with Jakafi (In­cyte’s rux­oli­tinib) in spleen re­duc­tion, but blew the key sec­ondary end­point of non-in­fe­ri­or­i­ty for the to­tal symp­tom score that was used to mea­sure the drugs. And it failed a sep­a­rate Phase III su­pe­ri­or­i­ty com­par­i­son against best avail­able treat­ment at week 24.

It all adds up to a fresh pipeline mess at Gilead, which saw its shares $GILD de­cline 1.25% Thurs­day morn­ing, shav­ing off more than a bil­lion dol­lars of its $100 bil­lion mar­ket cap. In­cyte {IN­CY}, mean­while, saw its shares shoot up 7% on the news, as spec­u­la­tion mount­ed that Gilead may now be pressed hard to make a bid for the com­pa­ny.

By the num­bers: mo­melo­tinib: 6.7%; BAT: 5.8%; 95 per­cent CI: -8.9% to +10.2%; p=0.90. And be­cause it didn’t suc­ceed on su­pe­ri­or­i­ty on the pri­ma­ry score, in­ves­ti­ga­tors didn’t run the num­bers on sec­ondary end­points.

That’s not what the com­pa­ny want­ed or need­ed to see. But af­ter high­light­ing some pos­i­tive trends from the two late-stage stud­ies, Gilead plans to see if reg­u­la­tors are feel­ing gen­er­ous about its prospects.

“The re­sults from both the SIM­PLI­FY-1 and SIM­PLI­FY-2 stud­ies in­di­cate that mo­melo­tinib pro­vides some treat­ment ben­e­fit, in­clud­ing ben­e­fit on ane­mia-re­lat­ed end­points,” said Nor­bert Bischof­berg­er, PhD, Ex­ec­u­tive Vice Pres­i­dent of Re­search and De­vel­op­ment and Chief Sci­en­tif­ic Of­fi­cer. “We plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps.”

The set­back on mo­melo­tinib comes near the end of what has turned in­to a grim year for Gilead. A re­cent run­down of its work on the NASH drug GS-4997 sparked con­sid­er­able skep­ti­cism from an­a­lysts, who want to see much more com­pelling num­bers be­fore they buy in.

Gilead re­cent­ly wrote off sim­tuzum­ab, along with the late-stage drug GS-5745 for ul­cer­a­tive col­i­tis and Crohn’s. And it’s top car­dio prospect — ele­clazine (GS-6615) — failed a late-stage study as well, sig­nif­i­cant­ly re­duc­ing its chances of be­com­ing the big new drug that Gilead needs as hep C wanes.

As the R&D hole keeps get­ting deep­er, some won­der if Gilead will be forced back to the deal ta­ble to buy some­thing big. Its hep C fran­chise may be wan­ing, but it cre­at­ed a huge wind­fall in cash re­serves. And Leerink’s Ge­of­frey Porges be­lieves that this lat­est black cloud comes with a sil­ver lin­ing, adding In­cyte to the list of big takeover tar­gets. On Thurs­day morn­ing he not­ed:

GILD in­di­cat­ed that they plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps, but it seems like­ly that mo­melo­tinib, which has been in de­vel­op­ment since 2009, will be writ­ten off, end­ing the po­ten­tial of yet an­oth­er small “bolt on” ac­qui­si­tion. One con­se­quence of this dis­ap­point­ment, how­ev­er, is that it does re­store IN­CY to the list of fea­si­ble can­di­dates for ac­qui­si­tion by Gilead, since they would no longer face the oblig­a­tion to di­vest one of the over­lap­ping JAK pro­grams.

The EMA released updated recommendations today for the use of JAK inhibitors (JAKi) after reviewing data from several clinical trials that showed increased incidents of issues in certain patients who have rheumatoid arthritis and other risk factors.

The EMA noted malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality in some patients.