SMUG1

Re­searchers spent close to a decade look­ing for signs that the failed Alzheimer’s drug crenezum­ab might work in a study that re­strict­ed it­self to a group of fam­i­lies with a rare ge­net­ic mu­ta­tion that left them sus­cep­ti­ble to ear­ly-on­set dis­ease. Bioreg­num Opin­ion Col­umn by John Car­roll It failed. And to­day we’re get­ting a bet­ter look at just how bad the da­ta are — and a biotech’s will­ing­ness to tout it any­way as AC Im­mune takes its turn at the Alzheimer’s As­so­ci­a­tion In­ter­na­tion­al Con­fer­ence. PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead AC Im­mune $ACIU post­ed three p-val­ues for cog­ni­tive scores com­pared to place­bo: 0.43, 0.16 and 0.55. Here’s its score on clin­i­cal/func­tion val­ues: Time to MCI/de­men­tia due to AD 20.8% (p=0.48); time to non-Ze­ro in CDR-GS 8.1% (p=0.76); CDR Sum of Box­es 8.8% (p=0.64). Bio­mark­er end­points all failed, for amy­loid be­ta and tau, straight down the line on PET and CSF mea­sures. In its fa­vor, the drug looked clean on ARIA-E, a big safe­ty is­sue in the field. But be­ing safe doesn’t win much mar­ket share for drugs that aren’t proven to work, par­tic­u­lar­ly af­ter the Aduhelm fi­as­co . From the state­ment: PET mea­sures: Aβ PET SU­VR 3.6% (p=0.69); Tau-PET SU­VR 51.1% (p=0.20); FDG PET SU­VR 18.1% (p=0.25) CSF mea­sures: t-tau 28.7% (p=0.53); p-tau-181 37.4% (p=0.28); NfL 18.2% (p=0.46) AC Im­mune has a lot at stake, as Roche has to de­ter­mine whether or not the lat­est round on crenezum­ab’s fail­ure will put the last nail in the cof­fin for the ef­fort. It has a huge risk fac­tor at play with its oth­er big Alzheimer’s drug, gan­tenerum­ab, which reads out lat­er in the year af­ter its own ear­li­er flop . Roche pulls an­oth­er ma­jor piece out of the wob­bly Alzheimer's jen­ga, shut­ter­ing crenezum­ab PhI­I­Is But for AC Im­mune CEO An­drea Pfeifer, that da­ta pro­file still earns a big en­dorse­ment as both “en­cour­ag­ing and im­por­tant.” She adds: Giv­en the con­sis­ten­cy of re­sults fa­vor­ing crenezum­ab over place­bo, and the slow­er than ex­pect­ed de­cline in the place­bo group as mea­sured by the API ADAD com­pos­ite score, the nu­mer­i­cal dif­fer­ences seen in clin­i­cal and bio­mark­er analy­ses pro­vide in­trigu­ing ev­i­dence of po­ten­tial ac­tiv­i­ty im­pact­ing the path­o­gen­ic path­way. These re­sults, to­geth­er with the tri­al’s re­mark­able safe­ty da­ta show­ing no cas­es of ARIA-E over the eight-year tri­al, sup­port the de­ci­sion to al­low for the con­tin­ued treat­ment of mu­ta­tion car­ri­ers with crenezum­ab while fur­ther analy­sis of the da­ta is on­go­ing. AC Im­mune’s stock was up about 3% to­day, af­ter falling 79% since the IPO.