New SMA1 Gene Therapy Trial Begins, Aiming for Safer, Targeted Treatment

PHILADELPHIA, PA – February 26, 2026 – A new chapter of hope has opened for families affected by Spinal Muscular Atrophy Type 1 (SMA1), the most severe form of the inherited neurodegenerative disease. Philadelphia-based GEMMA Biotherapeutics announced today that the first infant has been dosed in its Phase 1/2 CHARISMA clinical trial for GB221, an investigational, next-generation gene therapy.

The landmark trial, conducted in Brazil, marks the first clinical evaluation of a gene therapy for SMA1 delivered directly into the cerebrospinal fluid (CSF) via an intracisterna-magna (ICM) injection. This novel approach, combined with a re-engineered genetic payload, aims to overcome some of the significant challenges associated with existing treatments for the devastating condition.

A Next-Generation Approach to a Devastating Disease

Spinal Muscular Atrophy is a progressive disease caused by a mutation in the SMN1 gene, which is essential for the survival of motor neurons that control muscle movement. In its most aggressive form, SMA1, symptoms appear before six months of age. Without treatment, infants progressively lose the ability to breathe and swallow, rarely surviving past 18 months.

GB221 is a one-time gene therapy designed to deliver a functional copy of the SMN1 gene directly to the central nervous system. What sets it apart as "next-generation" is its innovative delivery and design. Unlike the first-generation gene therapy for SMA, which is administered intravenously (IV) and requires high doses that circulate throughout the body, GB221 uses a targeted ICM injection. This method delivers the therapy directly into the fluid-filled space at the base of the brain, allowing for broad distribution throughout the brain and spinal cord.

This targeted delivery may allow for a significantly lower dose of the therapy, potentially reducing the risk of systemic side effects, particularly liver toxicity, which has been a concern with high-dose IV gene therapies. Furthermore, GB221 utilizes a proprietary modified transgene expression cassette, developed by a team led by gene therapy pioneer Dr. James M. Wilson at the University of Pennsylvania. This cassette is engineered to reduce the risk of toxicities related to the overexpression of the SMN protein and to mitigate potential sensory neurotoxicity.

"The medical team is monitoring the first patient carefully, hoping to see therapeutic benefit and progress towards developmental milestones," said Dr. Jonas Morales Saute, a principal investigator on the trial at the Hospital de Clínicas de Porto Alegre in Brazil. "We are excited to leverage our experience in genetic diseases and clinical research to accelerate the development and evaluation of genetic medicines for other rare diseases."

The Evolving Landscape of SMA Treatment

The development of GB221 comes at a time when the treatment landscape for SMA has already been transformed. The introduction of three approved therapies—Spinraza, Zolgensma, and Evrysdi—has fundamentally changed the prognosis for patients, turning a once-fatal disease into a manageable, though still challenging, chronic condition.

Spinraza (nusinersen) and Evrysdi (risdiplam) are splicing modifiers that work by helping the body use a backup gene, SMN2, to produce more functional SMN protein. Zolgensma (onasemnogene abeparvovec), like GB221, is a gene replacement therapy. However, its initial approval was for IV delivery in children under two, with an intrathecal version recently approved for older patients.

GEMMABio's approach with GB221 seeks to build upon these advances by creating a potentially safer and more refined gene therapy option specifically for the youngest and most vulnerable patients. By targeting the central nervous system directly and using a cassette designed for safety, the therapy could represent a significant step forward in optimizing treatment for infants with SMA1. The CHARISMA trial will evaluate the safety, tolerability, and efficacy of this approach in both symptomatic and presymptomatic infants.

A Global Partnership Paving the Way in Brazil

The decision to launch the CHARISMA trial in Brazil is a key element of GEMMABio's global strategy, highlighting a unique public-private partnership model aimed at expanding access to advanced medicines. The trial is a core component of a 2024 agreement between GEMMABio and the Oswaldo Cruz Foundation (Fiocruz), a major public health institution linked to the Brazil Ministry of Health.

Under the agreement, Fiocruz is investing up to $100 million over four years to fund clinical research and manufacturing activities in Brazil, positioning the country as a regional hub for GEMMABio's gene therapy programs in Latin America. This collaboration aims to not only accelerate clinical development but also ensure that these cutting-edge therapies become accessible and affordable through Brazil's public healthcare system.

"I would like to express our gratitude for the young child and family who were courageous in being the first to accept our investigational gene therapy for SMA1," said Dr. James M. Wilson, CEO of GEMMABio. He emphasized appreciation for the "tremendous potential of international public-private partnerships" with partners like Fiocruz, Brazil's health ministry, and the local medical teams.

Fiocruz President, Dr. Mario Moreira, highlighted the broader impact of the collaboration. "The ongoing clinical study opens a front of action that can transform the lives of families and children who deal with the disease on a daily basis," he stated. "The technology incorporation agreement also guarantees the opening of pathways for access to an innovative gene therapy for the first time in the Unified Health System."

FDA Incentives Fueling Pediatric Innovation

In a concurrent development that underscores the therapy's potential, the U.S. Food and Drug Administration (FDA) has granted GB221 a Rare Pediatric Disease Designation (RPDD). This designation is intended to encourage the development of new treatments for serious and life-threatening diseases that primarily affect children.

The designation makes GEMMABio eligible to receive a Priority Review Voucher (PRV) if GB221 is eventually approved by the FDA. A PRV can be used to shorten the FDA review time for a future drug from the standard ten months to just six. More importantly, these vouchers are transferable and can be sold to other pharmaceutical companies, representing a significant financial asset. In recent years, PRVs have sold for an average of over $100 million.

This powerful incentive was recently secured when the U.S. Congress reauthorized the PRV program through September 2029, providing a clear financial pathway for companies like GEMMABio to invest in high-risk, high-reward research for diseases that affect small patient populations.

The journey of GB221 from the laboratory to this first-in-human trial is the culmination of decades of foundational research. GEMMABio itself is a recent spin-off from the University of Pennsylvania's renowned Gene Therapy Program, with Dr. Wilson transitioning from his long-time academic role to lead the new company. The proprietary technology at the heart of GB221 was licensed from the university, which retains an equity interest in the company. As the CHARISMA trial now moves forward in Brazil, it represents a critical test of not only a next-generation therapy but also a new model for making life-changing genetic medicines a global reality.