These days mixed data in Alzheimer’s disease are enough to send a company’s stock rocketing. Today, AC Immune was the beneficiary after claiming a win in the phase 2 Lauriet trial of its tau-targeting agent semorinemab.
A closer look shows that the results are far from convincing. The placebo-controlled study, in mild-to-moderate Alzheimer’s patients, hit one primary endpoint but failed the other, and also missed its secondary efficacy endpoints. Perhaps this is enough to warrant further investigation, but pushing straight into a large phase 3 trial might be a rash move.
Another reason for caution is that semorinemab has already flunked a different mid-stage trial, Tauriel, in prodromal-to-mild patients.
AC Immune, to its credit, was up front about the equivocal Lauriet results. The group has not laid out its next steps, aside from saying that its partner Roche would continue analysing the results, and that an open-label portion of the study would continue as planned.
Still, the news was enough to send the group’s stock up 72% at the open this morning.
Lauriet had two co-primary endpoints: change in Adas-Cog11, which measures cognitive function, and change in ADCS-ADL, which measures functional capacity, at week 49. It hit only the first of these, with semorinemab showing a 44% reduction in Adas-Cog11 versus placebo.
Secondary endpoints included the mini-mental state examination (MMSE) and clinical dementia rating-sum of boxes (CDR-SB).
AC Immune’s chief executive, Andrea Pfeifer, noted that this was the first time an anti-tau monoclonal antibody had shown a therapeutic effect; however, she also acknowledged that the group was “still cautious about what this may mean for patients” given the miss on other endpoints.
Topline data are set to feature at the Clinical Trials on Alzheimer's Disease conference in November.
AC Immune is particularly invested in tau, with three other projects in clinical development. Other companies in this space have not fared well lately, with Biogen discontinuing gosuranemab in June, and Abbvie using its second-quarter earnings to disclose that it had dropped ABBV-8E12 after that project disappointed in phase 2.
But Biogen has other clinical-stage irons in the tau fire too, the table below shows, as well as the preclinical project ST-501, licensed from Sangamo.
Perhaps AC Immune’s result will give the other players here a boost, but it seems premature to declare the tau hypothesis back on just yet.
|Selected tau-targeting projects in clinical development|
|LMTM/TRx0237||Taurx Pharmaceuticals||Tau aggregation inhibitor||Lucidity trial completes Jun 2022|
|Semorinemab/RG6100||Roche/AC Immune||Anti-tau MAb (targets N-terminus)||Sep 2020: failed Tauriel in prodromal/mild Alz; Aug 2021: met one co-primary in Lauriet in mild/moderate Alzh|
|Zagotenemab/LY3303560||Lilly||Anti-tau MAb (targets N-terminus)||Early Alz study completed Aug 2021|
|Bepranemab/UCB0107||UCB/Roche||Anti-tau MAb (targets central region)||MCI/mild Alz study started Apr 2021; first data due H1'25|
|AADvac1||Axon Neuroscience||Anti-tau vaccine||Further development planned despite failure of ph2 Adamant trial|
|BIIB080/ IONIS-MAPTRx||Biogen/Ionis Pharmaceuticals||Tau antisense oligonucleotide RNAi therapeutic||Mild Alz study; part 1 showed safety/tolerability, part 2 ongoing|
|ACI-35.030||AC Immune/Johnson & Johnson||Anti-tau vaccine||Interim data from early Alz study reported Feb 2021; high-dose data due Q4'21|
|JACI-35.054||AC Immune/Johnson & Johnson||Anti-tau vaccine||
Early Alz study; higher dose started
|PNT001||Pinteon Therapeutics||Anti-tau MAb (targets cis-pT231 tau)||Healthy volunteer study reported Feb 2021; acute brain injury study initiated|
|ACI-3024||AC Immune/Lilly||Tau aggregation inhibitor||Ph1 completed; focus now on rare tauopathies|
|BIIB076||Biogen/Eisai||Anti-tau MAb (targets central region)||Healthy volunteer/Alz pts study completed Mar 2020; still in Biogen's pipeline|
|E2814||Eisai||Anti-tau MAb (targets microtubule binding region)||Healthy volunteer study completes Sep 2021; selected for Dian-Tu tau study Mar 2021|
|BEY2153||Beyondbio||Beta-amyloid & tau aggregation inhibitor||Healthy volunteer study completes Oct 2021|
|Lu AF87908||Lundbeck||Anti-tau MAb (targets C-terminus)||Healthy volunteer/Alz pts study recruiting|
|PRX005||Prothena/Bristol Myers Squibb||Anti-tau MAb (targets microtubule binding region)||Ph1 begun & Bristol opt-in June 2021|
|Source: EvaulatePharma & clinicaltrials.gov.|