REGENXBIO Announces Regulatory Update on Ultra Rare MPS Programs

Jan 28, 2026 at 7:30 AM EST PDF Version ROCKVILLE, Md., Jan. 28, 2026 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced that the U.S. Food and Drug Administration (FDA) placed a clinical hold on its investigational gene therapy, RGX-111, for the treatment of MPS I, also known as Hurler syndrome, following preliminary analysis of a single case of neoplasm (intraventricular CNS tumor) in a participant treated in its Phase I/II study. The FDA also placed a clinical hold on RGX-121, for the treatment of MPS II, also known as Hunter Syndrome, citing the similarities in products, study populations, and shared risk between the clinical studies.

The case was identified during a routine brain MRI of an asymptomatic five-year-old participant who received intracisternal RGX-111 four years prior. Preliminary genetic analysis of the resected tumor detected an AAV vector genome integration event associated with overexpression of a proto-oncogene (PLAG1), which is known to be susceptible to chromosomal rearrangements. The investigation to determine if this SAE is drug related is ongoing. The causality has not been established. The participant continues to be asymptomatic, with positive developmental advancements noted by the treating physician. No evidence of neoplasm has been reported in the nine other participants treated with RGX-111 nor in the 32 participants treated with RGX-121.

"We are surprised by FDA's decision to place our RGX-121 program on hold while the investigation of this single, inconclusive incident in RGX-111 continues," said Curran Simpson, President and CEO of REGENXBIO. "These are separate therapies, and the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged. Patient safety is our top priority, and we, our investigators, and the patient community remain confident in the benefit-risk ratio of RGX-121 and are highly encouraged by the meaningful efficacy profile demonstrated in the pivotal trial. RGX-121 presents an opportunity to address the urgent, significant unmet medical need in this ultra-rare disease community, and continued delay means continued neurodevelopmental decline in boys with MPS II."

REGENXBIO has not yet received the full clinical hold letter and awaits additional details from the FDA.

About RGX-121 (clemidsogene lanparvovec)

RGX-121 is a potential one-time gene therapy for the treatment of boys with MPS II, designed to deliver the iduronate-2-sulfatase (IDS) gene to the central nervous system (CNS). Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted iduronate-2-sulfatase (I2S) protein beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 expressed protein is structurally identical to normal I2S.

RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.

About Mucopolysaccharidosis Type II (MPS II)

MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme I2S leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate CSF HS D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder.

About RGX-111

RGX-111 is designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene to the central nervous system (CNS). Delivery of the IDUA gene within the cells in the central nervous system (CNS) could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. By providing rapid IDUA delivery to the brain, RGX-111 could potentially help prevent the progression of cognitive deficits that otherwise occurs in MPS I patients. RGX-111 has received orphan drug product, rare pediatric disease and Fast Track designations from the FDA.

About Mucopolysaccharidosis Type I (MPS I)

MPS I is a rare autosomal recessive genetic disease caused by a deficiency in the lysosomal enzyme alpha-L-iduronidase (IDUA), leading to an accumulation of glycosaminoglycans (GAGs) including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). This can include excessive accumulation of fluid in the brain, spinal cord compression, and cognitive impairment. MPS I is estimated to occur in 1 in 100,000 births. Current disease modifying therapies for MPS I include hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy with a recombinant form of human IDUA administered intravenously. However, intravenous enzyme therapy does not treat the CNS manifestations of MPS I, and HSCT can be associated with clinically significant morbidity and mortality. Key biomarkers of IDUA enzymatic activity in MPS I patients include its substrate heparan sulfate (HS), which has been shown to correlate with neurocognitive manifestations of the disorder.

ABOUT REGENXBIO Inc.

REGENXBIO is a biotechnology company on a mission to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the field of AAV gene therapy. REGENXBIO is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202 for the treatment of Duchenne; NAVSUNLI for the treatment of MPS II and RGX-111 for the treatment of MPS I, both in partnership with Nippon Shinyaku; and surabgene lomparvovec (ABBV-RGX-314) for the treatment of wet AMD and diabetic retinopathy, in collaboration with AbbVie. Thousands of patients have been treated with REGENXBIO's AAV platform, including those receiving Novartis' ZOLGENSMA®. REGENXBIO's investigational gene therapies have the potential to change the way healthcare is delivered for millions of people. For more information, please visit www.REGENXBIO.com.

FORWARD-LOOKING STATEMENTS

This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations, clinical trials, costs and cash flow. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timing or likelihood of payments from AbbVie or Nippon Shinyaku, the monetization of any priority review voucher, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. Refer to the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of REGENXBIO's Annual Report on Form 10-K for the year ended December 31, 2024, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the SEC and are available on the SEC's website at WWW.SEC.GOV. All of the forward-looking statements made in this press release are expressly qualified by the cautionary statements contained or referred to herein. The actual results or developments anticipated may not be realized or, even if substantially realized, they may not have the expected consequences to or effects on REGENXBIO or its businesses or operations. Such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Readers are cautioned not to rely too heavily on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this press release. Except as required by law, REGENXBIO does not undertake any obligation, and specifically declines any obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Zolgensma® is a registered trademark of Novartis Gene Therapies. All other trademarks referenced herein are registered trademarks of REGENXBIO.

REGENXBIO Inc. (RGNX) — FDA places two MPS programs on clinical hold

What Happened

Regulatory action: On January 28, 2026, REGENXBIO reported that the U.S. Food and Drug Administration (FDA) placed RGX-111 for mucopolysaccharidosis type I (MPS I; Hurler syndrome) and RGX-121 (clemidsogene lanparvovec) for mucopolysaccharidosis type II (MPS II; Hunter syndrome) on clinical hold, constraining both programs pending FDA-defined requirements. (1) (2) (8) (9)
Regulatory Update Details: The company attributed the RGX-111 hold to preliminary analysis of a central nervous system (CNS) tumor case and said FDA cited product and study-population similarities and shared risk in placing RGX-121 on hold. RGX-121’s biologics license application (BLA) had a previously stated Prescription Drug User Fee Act (PDUFA) target date of February 8, 2026, 11 days after the announcement; the release did not confirm whether the BLA review continued or whether that target remained operative. RGX-111 is a Phase I/II program with no marketing application or PDUFA date established. (1) (3) (8)

Trading Background

RGNX showed a strong but volatile advance, rising from $13.16 on October 28, 2025 to $15.98 on January 22, 2026, before dropping sharply to $13.41 by January 27; the largest late move was a 13.705% decline on January 23. Several other ≥7% moves occurred during the period without definitive company-specific catalysts being identified. The January 23–27 period should be flagged as timeline-sensitive, because the January 28 8-K lists January 23 as the “date of earliest event reported,” although the clinical holds were not publicly announced until January 28 at 7:30 a.m. EST. (1) (2)

Confirmed Information Based on Disclosures

Tumor finding and causality: The company reported that preliminary genetic analysis of the tumor detected an adeno-associated virus (AAV) vector genome integration event associated with overexpression of the proto-oncogene PLAG1. The investigation was ongoing, and causality had not been established. (1)
Observed cases in the treated cohorts: The company reported no other neoplasm cases among the nine other RGX-111 participants or the 32 RGX-121 participants it cited. (1)

Key Missing Information

Hold requirements and RGX-121 review status: The specific requirements and closure criteria in the full hold letters, and whether FDA requires resolution before action on the RGX-121 BLA or has changed its review schedule, are not disclosed. Therefore, it is not possible to determine whether existing-data responses could preserve the current-cycle path or whether a longer evidence path or review reset is required. (1) (2)

Company's Response

The company said its investigation into whether the RGX-111 tumor was drug-related was ongoing and that it was awaiting further FDA details after not yet receiving the full hold letter. No completed response or FDA-accepted remediation was reported. Management characterized RGX-121’s safety profile as unchanged and expressed confidence in its benefit-risk profile and pivotal-trial efficacy; these are company views, not separate FDA conclusions. (1)

News Release Framing Risks

The sentence “These are separate therapies, and the positive safety profile of RGX-121 in more than 30 patients treated, including those dosed nearly seven years ago, remains unchanged” combines the company’s characterization of the therapies as separate with reassurance about RGX-121’s safety. This could suggest that the RGX-111 case has little relevance to RGX-121, although the release says FDA cited product and study-population similarities and shared risk in placing RGX-121 on hold. The company’s characterization does not establish that FDA accepts its safety conclusion or resolve the basis and scope of the shared-risk concern. (1)

The sentence “Patient safety is our top priority, and we, our investigators, and the patient community remain confident in the benefit-risk ratio of RGX-121 and are highly encouraged by the meaningful efficacy profile demonstrated in the pivotal trial” emphasizes confidence and efficacy without providing supporting details or explaining how that view addresses the hold. In context, it may reassure readers about overall benefit-risk despite the unresolved safety question prompting regulatory action. The release does not establish that the company’s confidence resolves that question or provide the details needed to assess the broad efficacy characterization. (1)

Analytical Interpretation

Pre-event expectation snapshot: Immediately before the event, the supported trajectory was an FDA action on RGX-121’s pending BLA around February 8, 2026—not a guaranteed approval—while RGX-111 had no established dated milestone; management expected current-plan cash to fund operations into early 2027, excluding contingent partner milestones and potential RGX-121 voucher proceeds. (3) (4) (8)
Post-event change of expectation: The reported holds add a material safety-response burden to RGX-121’s near-term BLA path and constrain RGX-111 clinical progression, reducing RGX-121 timing and outcome certainty without establishing a revised PDUFA date or final FDA result. (1) (2)
Integrated assessment:
- The primary near-term exposure is RGX-121: the company-reported FDA shared-risk rationale links the RGX-111 case to RGX-121 based on product and study-population similarities, adding a safety-response control point to a BLA target 11 days away. RGX-111 faces a separate constraint on Phase I/II progression, but its pre-event status does not support a reliable before-and-after comparison. (1) (2) (3) (8)
- The preliminary integration finding associated with PLAG1 makes a vector-related biological mechanism plausible enough to investigate, but does not establish treatment causality or incidence. The reported regulatory bridge reaches RGX-121; it does not establish equivalent clinical risk in that program. (1)
- The sponsor-reported absence of neoplasm in 32 RGX-121 participants and nine other RGX-111 participants is a counter-signal against an already-observed broader case pattern, not proof that rare or delayed risk is absent. Prior follow-up reported for an eight-participant RGX-111 record—seven to 103 weeks—does not span the four-year interval before the reported tumor and may not answer a latency-related FDA question. (1) (7)
- The clinical holds constrain the programs but do not establish that FDA suspended the RGX-121 BLA review or changed its target date. Timing certainty has declined because an undefined response may have to be addressed within the remaining 11 days; outcome certainty has separately declined because the safety issue is now a regulatory control point, without establishing approval, a Complete Response Letter (CRL), or a final benefit-risk conclusion. (1) (2) (3)
- If FDA permits an existing-data response for RGX-121, the work could include compiling and analyzing safety follow-up, making a requested product and population comparison, and submitting a written response, followed by FDA assessment. If FDA instead requires evidence unavailable from existing records before BLA action, continued follow-up or a new prospective evidence package would need to be defined, executed, analyzed, submitted, and reviewed; that sequence cannot fit the 11-day window. No company-specific cost or applicable benchmark is available for either path, so the direct expense cannot be quantified. (1) (2)
- For RGX-111, the reported ongoing work is completion of the tumor and causality investigation and compilation of existing participant safety records, followed by any FDA-requested response and FDA assessment. If those records are insufficient, additional work could involve continued participant follow-up or new prospective evidence; the design and observation horizon are undefined, and no applicable cost benchmark is available. Any prolonged path would extend the period before clinical progression can resume. (1) (8)
- As of September 30, 2025, reported cash, cash equivalents and marketable securities of $302.0 million were about 2.4 times current liabilities of $124.6 million and 5.4 times the absolute value of one quarter’s approximately $56.5 million free-cash-flow outflow. Cash, cash equivalents and marketable securities had fallen about 17% from June 30, while cash flow remained negative. These comparisons indicate a meaningful near-term buffer for bounded work, not a forecast or proof that a prolonged path is funded through the next milestone. (4) (5) (6)
- In the quarter ended September 30, 2025, company-wide revenue of $29.7 million was about 36% of operating expenses of $82.1 million, including $56.1 million in research and development (R&D) expense. These figures are not attributed to the MPS programs; the holds do not establish current MPS product-revenue loss or an event-driven expense increase. A prolonged path could defer output from the existing cost base and potential operating leverage rather than establish permanent value loss. (4) (5)
- The full hold letters and FDA’s determination of whether existing records suffice will distinguish existing-data resolution from additional-evidence paths. The supported regulatory bridge stops at RGX-121; the evidence does not extend the event to RGX-202, broader company revenue, or a change in contractual payments. (1) (2) (5)
- Overall implication of this event: The holds materially reduce the timing and certainty of RGX-121’s near-term regulatory value inflection and constrain RGX-111 progression; current liquidity supports bounded work, but continuing negative cash generation increases sensitivity if FDA requires a prolonged evidence path. (1) (2) (4) (5) (6)