mvdln schreef op 13 oktober 2020 16:18:
Concurrent IONS (antisense) heeft vandaag positieve interim resultaten gepubliceerd voor hun ENaC target.
Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), the leader in antisense therapeutics, announced today that data from a clinical trial of IONIS-ENAC-2.5Rx demonstrated a significant decrease in the expression of epithelial sodium channel (ENaC) in subjects with cystic fibrosis (CF). The study showed a mean 55.6 percent decrease (p<0.05) in ENaC mRNA expression at the 75 mg dose in the multidose segment of the trial. The study represents the first time an antisense medicine delivered directly to the lung via a nebulizer has shown a significant reduction in ENaC messenger RNA levels. In preclinical studies, ENaC mRNA reductions of 40 percent or more resulted in significant improvement in mouse models of CF lung disease.
Wat is het belang van deze uitkomst voor ARWR? Wel, ARO-ENaC gebruikt dezelfde manier van overbrengen van hun target naar de longen. Hierdoor weten we eigenlijk vandaag al dat ARO-ENaC proof of concept een feit is! De vraag is alleen of ARO-ENaC een grotere reductie van ENaC bij CF patiënten kan verwezenlijken dan 55,6%, of het veilig(er) is en hoe lang er tussen de dosissen kan zitten.
The game is on! RNAi (ARWR) versus IONS (antisense).
Fro59 minutes ago
@Tad
Check out Arrowhead Events and Presentations May 21 2018 ....Poster presentation at ATS 2018 for rat model...looks like ENaC mRNA reduces lung expression by 60 and 72 percent
Intussen weten we dat ARWR meestal betere resultaten boekt bij menselijke targets dan bij dierlijke. Dat zou betekenen dat ARO-ENaC in H1/21 ergens interim data presenteert die dat van IONS overtreffen.
BioBoyScout1 hour ago
That's actually great news, as it helps establish proof of concept. Remember that Baird was skeptical about the success for ARO-ENaC in CF. While Ionis shows mRNA knockdown, I didn't see any discussion on how it actually helped CF patients. In the end, it looks like it will be a showdown between RNAi and antisense, with figuring out which one is more effective, for how long, and most importantly which one is the safest. If history is any indicator, we all know the answer to that one.