Neurogene

The FDA has placed a clinical hold on Rocket Pharmaceuticals' Phase II gene therapy trial for RP-A501 after a patient developed capillary leak syndrome and subsequently died.

• A newly released global clinical trials review provides extensive data on Interstitial Cystitis research, tracking trial numbers and enrollment trends across major countries worldwide. • The report categorizes trials by region, phase, status, and sponsorship, highlighting key pharmaceutical companies including Astellas Pharma, AbbVie, Johnson & Johnson, and Pfizer as prominent sponsors. • This comprehensive analysis serves as a strategic resource for stakeholders making investment decisions in IC research, offering insights into trial success rates and identifying optimal locations for clinical studies.

Neurogene has developed a monitoring and treatment algorithm designed to reverse hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory syndrome linked to high-dose AAV gene therapy.

A comprehensive 2025 pipeline analysis identifies over 20 companies developing more than 20 therapeutic candidates for Rett syndrome, highlighting significant industry investment in this rare neurological disorder.

• Neurogene has suspended enrollment in the high-dose arm of its NGN-401 gene therapy trial for Rett syndrome after a patient developed life-threatening systemic hyperinflammatory syndrome, a known risk with AAV vector therapies. • Despite early efficacy signals showing "meaningful gains of skills and developmental milestones" in low-dose patients, the company's shares plummeted nearly 44% following the safety concerns announcement. • The trial will continue with the low-dose cohort, though with delayed enrollment timeline, as the company works to balance promising efficacy data against serious safety considerations for this devastating neurological disorder.

• The FDA's START program, designed to expedite rare disease therapy development, has chosen its first candidates for enhanced guidance and support. • Denali Therapeutics' DNL12 for mucopolysaccharidosis IIIA, Neurogene's NGN-401 for Rett syndrome, and Larimar Therapeutics' nomlabofusp for Friedreich's ataxia are among the selected therapies. • Grace Science's GS-100 gene therapy for NGLY1 deficiency is also included, marking a significant step forward in addressing this life-threatening condition with no approved treatments. • The START program aims to provide comprehensive support in clinical trial design and data generation, facilitating efficient development of potentially life-saving therapies.

Novartis reports positive Phase 3 results for intrathecal onasemnogene abeparvovec (OAV101 IT) in spinal muscular atrophy (SMA) type 2 patients, showing promise in those aged 2-18.

• AbbVie's Vyalev, a 24-hour subcutaneous levodopa infusion, gained FDA approval for managing motor fluctuations in advanced Parkinson's, offering a novel therapeutic approach. • Intellia's CRISPR therapy, NTLA-2001, demonstrated safe redosing in ATTR amyloidosis patients, achieving additive pharmacodynamic effects on the target protein. • A phase 3 study revealed that buntanetap is a safe and well-tolerated drug which improves motor, nonmotor, and cognitive symptoms of Parkinson's disease. • The FDA supported using αSyn-SAA biomarker in Parkinson's clinical trials, enhancing therapeutic development through improved diagnostic precision.

• Two companies, Neurogene and Taysha Gene Therapies, are in Phase 1/2 clinical trials with gene therapies targeting the MECP2 gene for Rett syndrome. • These therapies aim to address the underlying genetic cause of Rett syndrome, unlike existing treatments that only manage symptoms. • Both companies have incorporated regulatory mechanisms to ensure precise MECP2 expression, avoiding complications from overexpression. • Preliminary data from ongoing trials are expected in late 2024 and early 2025, offering hope for a potential disease-modifying treatment.

• Cerevance's solengepras (CVN424) has entered a Phase 3 trial (ARISE) as an adjunctive therapy for Parkinson's disease, with topline data expected in the first half of 2026. • Sage Therapeutics discontinued the development of SAGE-718 (dalzanemdor) for Huntington's disease after disappointing Phase 2 results showing no significant cognitive improvement. • Neurogene paused the high-dose arm of its Phase 1 study of NGN-401, a gene therapy for Rett syndrome, following a serious adverse event in one participant.