Cell therapy weekly: IND clearance for pediatric central nervous system disease gene therapy
This week: the US Food and Drug Administration (FDA; MD, USA) cleared an Investigational New Drug (IND) application for a gene therapy indicated to treat an ultra-rare and fatal pediatric neurodegenerative disorder and granted Rare Pediatric Disease designation to an investigational gene therapy for Friedreich’s ataxia (FA). Plus, a Phase III trial assessing a cell therapy for Duchenne muscular dystrophy (DMD) met primary endpoint and secondary cardiac endpoint.
The news highlights:
- IND clearance for ultra-rare neurodegenerative disorder gene therapy
- Positive topline results from DMD Phase III cell therapy trial
- US FDA Rare Pediatrics Disease designation for FA gene therapy
IND clearance for ultra-rare neurodegenerative disorder gene therapy
The US FDA has issued an IND clearance for Latus Bio’s (PA, USA) LTS-101, a one-time adeno-associated virus (AAV) gene therapy intended to treat central nervous system manifestations of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease.
CLN2 is an ultra-rare and fatal neurodegenerative disorder that affects approximately 1 in 200,000 children worldwide. Due to a lack or loss of function in the tripeptidyl peptidase 1 enzyme, which helps break down and remove waste materials from neurons, patients begin experiencing developmental delays, loss of motor function, seizures and blindness from around age two. This condition typically reduces life expectancy to 8–12 years. Currently, the only approved treatment is an enzyme replacement therapy that requires regular infusions through a surgically implanted ventricular access device.
“FDA clearance of our first IND represents a major milestone for Latus,” commented P. Peter Ghoroghchian, CEO of Latus Bio. “The receipt of all possible FDA designations at this stage in development supports the promise of LTS-101 to address the urgent and unmet needs of children affected by CLN2 disease. It further underscores the potential of Latus’ novel AAV capsid discovery platform to yield transformative therapies that are enabled via one-time administration and at dramatically lower doses than are typically employed with conventional gene therapies.”
Alongside this IND clearance, the US FDA has also granted Orphan Drug, Rare Pedriatric Disease and Fast Track designations for LTS-101.
Positive topline results from DMD Phase III cell therapy trial
Biotechnology company Capricor Therapeutics (CA, USA) has announced positive topline results from its Phase III HOPE-3 trial evaluating Deramiocel – an investigational cell therapy for DMD. Deramiocel, also known as CAP-1002, comprises allogeneic cardiosphere-derived cells – a rare population of cardiac cells that act by secreting exosomes. These exosomes target and reprogram macrophages from a pro-inflammatory state to a healing state.
The trial demonstrated significant skeletal and cardiac benefits and maintained a favorable safety and tolerability profile consistent with previous clinical experience. The study met the primary endpoint and the secondary cardiac endpoint.
Craig McDonald, National PI of the HOPE-3 trial, commented on the meaningful and significant treatment effects on both upper limb function and cardiomyopathy, stating:
“A nearly 54 percent slowing of skeletal muscle disease progression is extraordinary in Duchenne and directly linked to maintaining independence and quality of life in the most severely affected patients with greatest unmet need. The preservation of function reflected in Performance of Upper Limb v2.0 translates into real, practical benefits for boys and young men living with this disease, and the effect of Deramiocel on cardiomyopathy will potentially translate to improved long-term survival.”
Deramiocel has been awarded Orphan Drug designation for the treatment of DMD by both the US FDA and the European Medicines Agency. Additionally, it has received Regenerative Medicine Advanced Therapy designation in the USA, Advanced Therapy Medicinal Product designation in Europe and Rare Pediatric Disease designation from the US FDA, which could qualify Capricor to receive a Priority Review Voucher upon approval.
US FDA Rare Pediatrics Disease designation for FA gene therapy
Solid Biosciences (MA, USA) announced that it has received a US FDA Rare Pediatric Disease designation for its investigational gene therapy, SGT-212, for FA. SGT-212 is a recombinant AAV-based gene replacement therapy designed to promote restoration of therapeutic levels of the frataxin protein to address neurologic, cardiac and systemic clinical manifestations of FA. The therapy delivers the complete frataxin gene through two delivery methods: direct intradentate nucleus infusion and intravenous infusion.
“Together with the Fast Track designation granted earlier this year, it recognizes our dual-route clinical approach for FALCON, our first-in-human trial, which is now screening participants, as an important first step in meeting an unmet need for FA. These designations are designed to help accelerate time to market and enhance engagement with the FDA,” remarked Solid Biosciences’ Chief Regulatory and Preclinical Operations Officer, Jessie Hanrahan. “We look forward to continued collaboration with regulators to bring this therapy to patients as quickly as possible.”
