#United States #Rockville #REGENXBIO #MPS I #MPS II

REGENXBIO Faces Regulatory Challenges: FDA Places Clinical Hold

In a significant regulatory development, REGENXBIO Inc. (Nasdaq: RGNX) announced today that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on its investigational gene therapy RGX-111, which aims to treat Mucopolysaccharidosis Type I (MPS I), also known as Hurler syndrome. This decision stems from the preliminary findings related to a serious adverse event (SAE) observed in a clinical trial participant, raising concerns about the safety profile of the treatment.

The hold also extends to RGX-121, a gene therapy for MPS II, known as Hunter syndrome, due to the similarities between the two products and potential risks inherent to both clinical studies. This cautionary approach by the FDA follows the identification of an intraventricular CNS tumor in a five-year-old who had previously received RGX-111. Although the case was noted during a routine MRI and the child remains asymptomatic, it has drawn scrutiny, especially after genetic analysis revealed an integration event of the adeno-associated virus (AAV) vector genome linked to overexpression of a proto-oncogene (PLAG1).

Curran Simpson, President and CEO of REGENXBIO, expressed surprise at the decision to suspend RGX-121, emphasizing the distinction between the two gene therapies and their individual safety profiles. He reassured stakeholders that RGX-121 has been administered to over 30 patients with no concerning safety issues, maintaining a robust efficacy profile demonstrated in pivotal trials. Simpson underscored the pressing need for effective treatments in the ultra-rare disease community, highlighting that such regulatory delays could hinder progress and worsen neurodevelopmental outcomes for boys suffering from MPS II.

"Patient safety is our top priority, and we, our investigators, and the patient community remain confident in the benefit-risk ratio of RGX-121," Simpson stated. This optimism comes from years of patient data indicating sustained positive results in those treated with RGX-121, including participants treated almost seven years ago.

Currently, REGENXBIO has yet to receive the full clinical hold letter and further details from the FDA regarding the investigation into RGX-111. The implications of this regulatory action could be profound for the field of gene therapy, particularly in the context of MPS disorders, which have limited treatment options available.

Understanding MPS Disorders

MPS II (Hunter Syndrome)

MPS II is an X-linked recessive disorder caused by an enzyme deficiency that leads to harmful accumulation of glycosaminoglycans (GAGs) in the body, particularly affecting the central nervous system and various other organs. Due to this enzyme deficiency, patients exhibit a range of symptoms, including developmental delays and cognitive impairment. Specific treatments addressing neurological manifestations of MPS II remain scarce, marking this an area of urgent unmet medical need.

MPS I (Hurler Syndrome)

Conversely, MPS I is also caused by an enzyme deficiency, which leads to comparable complications. The challenges associated with treating MPS I and MPS II often involve traditional methods such as hematopoietic stem cell transplants or enzyme replacement therapies, which do not adequately address CNS issues. Therefore, innovative gene therapies like RGX-111 and RGX-121 offer hope as potential transformative solutions for these disorders.

The Road Ahead for REGENXBIO

Moving forward, the company must navigate this regulatory landscape with care as it seeks to gather more clarity from the FDA. With its rich pipeline of AAV gene therapies, REGENXBIO continues to push boundaries in the biopharmaceutical industry, endeavoring to deliver effective treatments for conditions that have long been overlooked.

Despite the current challenges, REGENXBIO's commitment to advancing gene therapy solutions remains unwavering, as the company works to respond to FDA inquiries and provide necessary data to address safety concerns. The broader implications of these developments not only affect patients enrolled in clinical trials but also the future landscape of treatment options for rare diseases, emphasizing the importance of continued innovation in gene therapy.

For more information about REGENXBIO and its ongoing research, please visit www.REGENXBIO.com.