Rare neurodeg RNA/ASO/ERT approvals + new disorders + AI dx + LSD small-mols [climaxing]
Key Questions
What is Denali's Avlayah approval for MPS II?
Denali's Avlayah (tividenofusp alfa) received FDA accelerated approval as the first CNS-targeted ERT for MPS II (Hunter syndrome). It advances the pipeline alongside Homology's HMI-203 and JCR's pabinafusp.
What is the status of zilganersen for Alexander disease?
Ionis' zilganersen ASO for AxD has NDA under Priority Review by FDA. It targets GFAP reduction in this rare neurodevelopmental disorder.
What results did UVA's SCN8A base editing show in DEE mice?
UVA's base edit in SCN8A mice for developmental epileptic encephalopathy (DEE) made them seizure-free, improved survival/movement/anxiety, with toxicology next. It promises a transformative epilepsy treatment.
What is Neurocrine's acquisition of Soleno Therapeutics?
Neurocrine acquired Soleno for $2.9B, gaining VYKAT for Prader-Willi syndrome (PWS), a rare genetic neurodevelopmental disorder affecting ~10,000 in the US.
How effective was the Fabry single-dose stem cell therapy?
A Canadian CIHR-led trial showed single-dose stem cell therapy for Fabry disease was safe, allowing patients off ERT with stable kidney function for 3.5-6 years.
What are aiProtein GOF mRNA enzymes achievements?
aiProtein's gain-of-function mRNA enzymes are 8x more active and stable, overcoming protein replacement therapy challenges for lysosomal storage disorders (LSDs).
What challenges exist in platform trials for orphan diseases?
Platform trials face regulatory, financial, and access hurdles for rare diseases, including new LATAM challenges. Advances include ex vivo gene therapy and LSD small molecules like Polaryx/Aro Pompe.
What is relutrigine for developmental epileptic encephalopathy?
Relutrigine is advancing for DEE, alongside Spinraza for SMA and apitegromab BLA. Precision challenges persist in LGS and other epilepsies.
Denali Avlayah MPS II FDA accel approval first CNS ERT; Homology HMI-203 MPS II; JCR pabinafusp Japan; REGENXBIO RGX-121 CRL; Neurocrine $2.9B Soleno PWS VYKAT; Q1'26 Menkes copper survival; zilganersen AxD NDA Priority Review; Spinraza SMA; apitegromab BLA; relutrigine DEE; UVA SCN8A base edit mice seizure-free/survival++/movement/anx tox next; LGS precision challenges; Polaryx LSD; Aro Pompe; sildenafil Leigh; aiProtein GOF mRNA enzymes 8x active/stable; Fabry single-dose stem cell tx off ERT 3.5-6yrs kidney stable; platform trials orphan challenges LATAM.