After Vertex’s VX-864 crashed out in alpha-1 antitrypsin deficiency (AATD) earlier this year Arrowhead became the contender to watch – but early data from Dicerna today suggest that its rival RNAi project might also have legs. There are big caveats here: the release is thin on detail and concerns data in only 18 volunteers. But Dicerna’s belcesiran appears to produce dose-dependent declines in serum AAT, mutated forms of which build up in the liver and lungs of AATD sufferers, causing the rare inherited disease's severe complications. One subject in the 6mg/kg cohort registered a 91% decline, Dicerna said, adding that dosing had commenced at 12mg/kg. Perhaps the group feels the need to push harder to match the levels reported by Arrowhead with ARO-AAT, which sustained 78-97% reductions in mutated AAT over one year, data at Easl last month revealed. Belcesiran still needs to prove its worth in actual patients, and a phase 2 trial called Estrella has already started. But with Mereo’s MPH-966 the only other clinical AATD asset – phase 2 data are due by year end – Dicerna had good reasons to push on here.
|Joining the AATD race: phase 1 data on belcesiran (DCR-A1AT)|
|1mg/kg (n=6)||3mg/kg (n=6)||6mg/kg (n=4)||12mg/kg (n=6)|
|Mean maximum serum AAT reductions from baseline||50%||69%||80%||?|
|Source: Dicerna press release.|