Phar­ma­ceu­ti­cal com­pa­nies are on a deal­mak­ing tear.

Six phar­ma com­pa­nies have signed ac­qui­si­tions worth up to $25.5 bil­lion since the be­gin­ning of last week. Two $5 bil­lion-plus up­front deals were dis­closed on Tues­day morn­ing alone: Eli Lil­ly's bet on Centes­sa Phar­ma­ceu­ti­cal­s' orex­ins and Bio­gen's con­sum­ma­tion of com­mer­cial play­er Apel­lis Phar­ma­ceu­ti­cals. There were a to­tal of sev­en deals of that mag­ni­tude in all of 2025.

It's no sur­prise. Large drug­mak­ers are fill­ing their late-stage pipelines to fend off patent cliffs, padding out ear­li­er R&D en­gines to ex­tend their dom­i­nance in cer­tain fields and dou­bling down on emerg­ing ther­a­peu­tic class­es.

Across March, bio­phar­mas lined up 10 ac­qui­si­tions worth up to $31.5 bil­lion, ac­cord­ing to an End­points News tal­ly. Eight of those in­clud­ed con­tin­gent val­ue rights or mile­stone pay­ments re­liant on R&D or reg­u­la­to­ry achieve­ments, a deal­mak­ing struc­ture that has be­come more com­mon in re­cent years.

The FDA on Tues­day flagged more than 70 cas­es of se­vere liv­er in­jury and eight deaths as­so­ci­at­ed with Am­gen’s au­toim­mune treat­ment Tavneos, but the com­pa­ny said it pre­vi­ous­ly no­ti­fied the agency about the risk of one of the most se­vere cas­es.

The safe­ty da­ta from the FDA come as the agency and Am­gen spar over Tavneos’ fu­ture. The FDA asked Am­gen to pull the drug from the mar­ket in Jan­u­ary, which it has de­clined to do.

The FDA said in a new drug safe­ty com­mu­ni­ca­tion that it record­ed 76 cas­es of drug-in­duced liv­er in­jury through Oc­to­ber 9, 2024, in­clud­ing eight deaths. Of the 76 cas­es, sev­en were biop­sy-con­firmed cas­es of van­ish­ing bile duct syn­drome, all of which re­sult­ed in hos­pi­tal­iza­tion and three of which led to death. Al­most all of the liv­er in­jury cas­es were re­port­ed from Japan, with 10 cas­es com­ing from the US, Cana­da and Eu­rope.

As­traZeneca’s ex­per­i­men­tal en­zyme re­place­ment ther­a­py gen­er­at­ed mixed re­sults in three late-stage tri­als tar­get­ing a rare ge­net­ic con­di­tion called hy­pophos­phata­sia that can cause soft and weak bones.

The treat­ment, efz­im­fo­tase al­fa, is be­ing de­vel­oped as a next-gen­er­a­tion ver­sion of As­traZeneca’s block­buster drug Stren­siq to ex­tend the com­pa­ny’s dom­i­nance in hy­pophos­phata­sia, which af­fects about three in 100,000 peo­ple and can leave pa­tients with pain and fa­tigue, lost teeth and oth­er symp­toms.

On Tues­day, As­traZeneca said the ex­per­i­men­tal drug failed a Phase 3 tri­al in adults and ado­les­cents. But two oth­er tri­als had pos­i­tive read­outs.

The HICK­O­RY tri­al stud­ied hy­pophos­phata­sia pa­tients 12 years and old­er who had­n't pre­vi­ous­ly been treat­ed with Stren­siq, the on­ly ap­proved drug for the dis­ease. Efz­im­fo­tase al­fa showed an im­prove­ment com­pared with place­bo on a six-minute walk test — the tri­al’s pri­ma­ry end­point — but the dif­fer­ence wasn’t sta­tis­ti­cal­ly sig­nif­i­cant. As­traZeneca blamed “bet­ter-than-ex­pect­ed re­sults” in a place­bo group of adult-on­set pa­tients.

Eli Lil­ly is mak­ing its biggest ac­qui­si­tion in years, de­vot­ing part of its GLP-1 cash in­flux to buy Centes­sa Phar­ma­ceu­ti­cals and its ex­per­i­men­tal med­i­cines for sleep dis­or­ders and neu­ro­log­i­cal con­di­tions.

The phar­ma gi­ant will de­vote $6.3 bil­lion up­front and up to $1.5 bil­lion in con­tin­gent val­ue rights to ac­quire Centes­sa and its orex­in re­cep­tor 2 (OX2R) ag­o­nists. The deal is for $38 per share $CN­TA up­front in cash. It al­so in­cludes mul­ti­ple CVRs up­on cer­tain reg­u­la­to­ry ap­provals.

Centes­sa’s lead drug, called clemi­norex­ton (ORX750), is in Phase 2a test­ing for nar­colep­sy type 1, nar­colep­sy type 2 and id­io­path­ic hy­per­som­nia.

The ex­per­i­men­tal med­i­cine was ex­pect­ed to be­gin a reg­is­tra­tional tri­al in the first quar­ter, ac­cord­ing to a Feb­ru­ary cor­po­rate pre­sen­ta­tion. Oth­er OX2R ag­o­nists that could com­pete with it in­clude Take­da’s late-stage ove­porex­ton and Alk­er­mes’ mid-stage al­ixorex­ton. Centes­sa al­so has at least two oth­er OX2R ag­o­nists in ear­ly de­vel­op­ment.