Arrowhead previously played down hopes for its rare liver disease candidate ARO-AAT, so investors were pleasantly surprised by the limited data released yesterday. But it is hard to see why the group added $1.4bn in market cap on results that theoretically might have come from one patient. Arrowhead claimed to be reporting interim six-month liver biopsy data from four subjects in a phase II open-label study of ARO-AAT. The project is being developed for alpha-1 antitrypsin deficiency (AATD), a genetic disorder characterised by the build-up of mutant AAT protein (Z-AAT) in the liver. However, rather than reporting average values, Arrowhead only gave the best reported patient outcome for most endpoints – so, for example, serum and total intra-hepatic Z-AAT decreased by a maximum of 93% and 95% respectively. The group also reported a maximum 97% reduction in Z-AAT polymer – this was considered encouraging, since investors had previously been told that it might be too early to see a benefit here. This is no doubt what caused the excitement yesterday, but much more complete data are needed to draw reliable conclusions. Arrowhead hopes to present results from all four patients at the AASLD meeting in November; the pivotal Sequoia trial is ongoing.
|Selected AATD projects in development|
|ARO-AAT||Arrowhead Pharmaceuticals||RNAi therapeutic||Phase II/III, NCT03946449 & NCT03945292||Interim data reported|
|VX-814||Vertex Pharmaceuticals||Alpha-1 proteinase inhibitor||Phase II, NCT04167345||Data due YE 2020/Q1 2021|
|VX-864||Vertex Pharmaceuticals||Alpha-1 proteinase inhibitor||Phase II, NCT04474197||Trial began Jul 2020|
|DCR-A1AT||Dicerna Pharmaceuticals||RNAi therapeutic||Phase I/II, NCT04174118||Dicerna & Alnylam co-developing|
|ALN-AAT02||Alnylam Pharmaceuticals||RNAi therapeutic||Phase I/II, NCT03767829||Dicerna & Alnylam co-developing|
|Source: EvaluatePharma, clinicaltrials.gov.|