🧬 This Week in Rare Diseases: FDA Label Expansion, Accelerated Approvals, RNA Breakthroughs, and FOP Milestone
From the US to Australia and New Zealand, this week’s roundup spotlights pivotal regulatory moves, late-stage wins, and modality-first signals in ultra-rare diseases—spanning NF1-PN, DMD exon 44, TED, PKU/CKD, FOP, Barth syndrome, Alexander disease, and Huntington’s.
In Today’s Newsletter
🏛️ FDA expands selumetinib (KOSELUGO) to ≥1 year in NF1-PN [1] [US • 10 Sep 2025]
Context: Bridging BA (healthy adults) and exposure matching (SPRINT ≥2 yr capsules; SPRINKLE ≥1 yr granules); label carries cardiomyopathy/ocular/GI/skin/CK/vit E/bleeding and embryo-fetal warnings; no new safety signals.
Key point: FDA approved granules & capsules for pediatric patients ≥1 yr with symptomatic, inoperable NF1 plexiform neurofibromas (efficacy extrapolated).
Implication: Regulatory/generics: Introduces competition that may affect pricing and formulary access.
🧬 Del-zota (Avidity) reverses DMD44 progression in 1-yr Phase 1/2 update [2] [US • 10 Sep 2025]
Context: EXPLORE44/-OLE; ~25% normal dystrophin; CK ↓ >80% to near-normal up to 16 mo; mostly mild/moderate TEAEs; 1 hypersensitivity-related discontinuation.
Key point: Functional measures improved vs natural history at ~1 yr (e.g., TTR, 4SC, 10mWRT, PUL); BLA targeted YE 2025 (accelerated).
Implication: Clinical topline/efficacy: May influence prescriber choice and payer reviews pending full data.
👁️🗨️ Viridian completes Phase 3 enrollment for VRDN-003 in TED; veligrotug BLA on track [3] [US • 15 Sep 2025]
https://investors.viridiantherapeutics.com/news/news-details/2025/Viridian-Therapeutics-Announces-Completion-of-Enrollment-in-both-REVEAL-Clinical-Trials-and-Positive-Portfolio-Updates/default.aspx
Context: REVEAL-1 (n=132, active) and REVEAL-2 (n=204, chronic) exceeded targets; majority US enrollment; portfolio updates on FcRn (VRDN-006/-008).
Key point: Topline for VRDN-003 H1 2026; veligrotug BLA anticipated Nov 2025 (BTD; Priority Review eligible).
Implication: Partnerships/BD: Signals pipeline investment and modality expansion.
🧪 Maze’s MZE782 hits proof-of-mechanism in Phase 1 (PKU/CKD) [4] [US • 11 Sep 2025]
https://ir.mazetx.com/news-releases/news-release-details/maze-therapeutics-announces-positive-first-human-results-phase-1
Context: Randomized SAD/MAD in 112 HVs; dose-dependent urinary Phe/Gln ↑ (up to 42x/68x); transient eGFR dip akin to SGLT2s; no SAEs.
Key point: Robust target engagement supports Phase 2 in 2026 for PKU (plasma Phe) and CKD (proteinuria).
Implication: Clinical topline/efficacy: May influence prescriber choice and payer reviews pending full data.
🧫 Garetosmab (Regeneron) meets Phase 3 in FOP, slashes new HO [5] [US • 17 Sep 2025]
Context: OPTIMA (n=63 adults). At 56 wks, new HO lesions ↓ 90–94% vs placebo; new HO volume ↓ ~99.8–99.9%; dose-related skin/soft-tissue infections noted; fewer MSK pain AEs.
Key point: First therapy to show marked reductions in both number and volume of new HO; US submission planned YE 2025.
Implication: Clinical topline/efficacy: May influence prescriber choice and payer reviews pending full data.
💉 Forzinity (Stealth) gets FDA accelerated approval for Barth syndrome [6] [US • 19 Sep 2025]
https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-first-treatment-rare-life-threatening-disease-males-2025-09-19/
Context: First approved therapy for Barth syndrome (primarily males); SC once-daily; benefit based on knee-extension strength.
Key point: Accelerated approval for patients ≥30 kg; confirmatory study required to verify clinical benefit.
Implication: Regulatory/generics: Introduces competition that may affect pricing and formulary access.
🧠 Zilganersen (Ionis) plans NDA after positive AxD Phase 1–3 data [7] [22 Sep 2025]
https://www.neurologylive.com/view/ionis-plans-application-submission-zilganersen-potential-first-treatment-alexander-disease-following-positive-data
Context: Double-blind controlled trial (n=54; ages 1.5–53). Higher dose showed 33.3% mean difference on 10-Meter Walk Test vs placebo (p=0.0412); other endpoints trended positive.
Key point: Ionis targets Q1 2026 NDA; US expanded access program planned.
Implication: Clinical topline/efficacy: May influence prescriber choice and payer reviews pending full data.
🧬 SKY-0515 (Skyhawk) lowers mHTT up to 62% at Day 84 in HD Phase 1 interim [8] [US • 17 Sep 2025]
https://www.prnewswire.com/news-releases/skyhawk-therapeutics-announces-positive-first-interim-results-in-patients-from-its-phase-1-clinical-trial-of-sky-0515-as-a-treatment-for-huntingtons-disease-302559083.html
Context: Part C patients (placebo n=6; 3 mg n=10; 9 mg n=10). Oral splicing modulator; dose-dependent mHTT↓ and PMS1 mRNA↓; favorable safety; CNS penetration.
Key point: 62% mHTT reduction at 9 mg by Day 84; Phase 2/3 FALCON-HD ongoing in Australia/New Zealand.
Implication: Clinical topline/efficacy: May influence prescriber choice and payer reviews pending full data.
Why it matters
- FDA actions (selumetinib, Forzinity) show extrapolation and accelerated pathways in ultra-rare pediatrics and mitochondrial disease.
- Garetosmab’s late-stage efficacy could reset expectations in skeletal ultra-rare FOP.
- RNA-targeted modalities (AOC, ASO, small-molecule splicing) are generating patient-relevant signals across DMD, AxD, and HD.
- Transporter biology (SLC6A19) opens metabolic/renal avenues with clear PD markers.
- TED competition is intensifying; multiple 2026 readouts/filings may shift payer dynamics.
📢 Stay Ahead in Rare Disease Research!
✅ Contact LucidQuest at info@lqventures.com for strategic guidance on orphan drugs, rare conditions, and clinical trial breakthroughs
FAQ
What changed in KOSELUGO’s US label?
FDA now includes pediatric patients ≥1 yr (granules & capsules) with symptomatic, inoperable NF1 plexiform neurofibromas, based on formulation bridging and exposure matching; no new safety signals. [1]
How strong are del-zota’s DMD44 signals?
Company reports functional improvements vs natural history at ~1 yr, ~25% normal dystrophin, and CK reductions >80%, with generally mild/moderate AEs; BLA targeted YE 2025 (accelerated). [2]
What exactly did garetosmab achieve in FOP?
In OPTIMA Phase 3, new HO lesions fell 90–94% vs placebo at 56 wks, with ~99.8–99.9% reductions in new lesion volume; US submission planned YE 2025. [5]
What is Forzinity’s approval based on?
FDA granted accelerated approval in Barth syndrome (≥30 kg) based on improved knee-extension muscle strength; confirmatory outcomes required. [6]
When will Ionis file for zilganersen?
Ionis plans a Q1 2026 NDA after a controlled study showed a 33.3% mean difference on 10-Meter Walk Test at the higher dose; other endpoints trended favorable. [7]
How far along is SKY-0515 in HD?
Phase 1 patient interim shows dose-dependent mHTT lowering (up to 62% at Day 84) with favorable safety; a Phase 2/3 trial is ongoing in Australia/New Zealand. [8]
Entities / Keywords
AstraZeneca; selumetinib (KOSELUGO); NF1; plexiform neurofibroma • Avidity Biosciences; del-zota; DMD exon 44; AOC • Viridian Therapeutics; VRDN-003; veligrotug; TED; FcRn • Maze Therapeutics; MZE782; SLC6A19; PKU; CKD • Regeneron; garetosmab; Activin A; FOP; heterotopic ossification • Stealth BioTherapeutics; Forzinity; Barth syndrome; accelerated approval • Ionis; zilganersen; Alexander disease; antisense • Skyhawk Therapeutics; SKY-0515; Huntington’s disease; RNA splicing.
References
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selumetinib-pediatric-patients-1-year-age-and-older-neurofibromatosis-type-1
- https://www.prnewswire.com/news-releases/avidity-biosciences-del-zota-demonstrated-reversal-of-disease-progression-across-key-functional-endpoints-in-explore44-and-explore44-ole-phase-12-trial-in-people-living-with-dmd44-302552339.html
- https://investors.viridiantherapeutics.com/news/news-details/2025/Viridian-Therapeutics-Announces-Completion-of-Enrollment-in-both-REVEAL-Clinical-Trials-and-Positive-Portfolio-Updates/default.aspx
- https://ir.mazetx.com/news-releases/news-release-details/maze-therapeutics-announces-positive-first-human-results-phase-1
- https://www.globenewswire.com/news-release/2025/09/17/3151506/0/en/Regeneron-Announces-Positive-Phase-3-Trial-in-Adults-with-Ultra-Rare-Genetic-Disorder-Fibrodysplasia-Ossificans-Progressiva-FOP-Demonstrating-that-Garetosmab-Prevents-Greater-than-.html
- https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-first-treatment-rare-life-threatening-disease-males-2025-09-19/
- https://www.neurologylive.com/view/ionis-plans-application-submission-zilganersen-potential-first-treatment-alexander-disease-following-positive-data
- https://www.prnewswire.com/news-releases/skyhawk-therapeutics-announces-positive-first-interim-results-in-patients-from-its-phase-1-clinical-trial-of-sky-0515-as-a-treatment-for-huntingtons-disease-302559083.html