REGENXBIO maps 2026 gene therapy milestones

REGENXBIO used its fourth-quarter and full-year 2025 earnings call to outline what management described as a pivotal year ahead as it advances late-stage gene therapy programs in Duchenne muscular dystrophy (DMD) and retinal disease. The company also detailed a series of 2026 milestones across Duchenne, wet age-related macular degeneration (wet AMD), and diabetic retinopathy, while addressing recent regulatory setbacks in mucopolysaccharidosis (MPS) programs.

Chief Executive Officer Curran Simpson and Chief Medical Officer Steve Pakola highlighted RGX-202 as REGENXBIO’s lead program, describing it as a potential best-in-class gene therapy for DMD. Dosing in the pivotal AFFINITY DUCHENNE trial was completed in October 2025, and a separate confirmatory study is said to be enrolling robustly.

Top-line data from the pivotal AFFINITY DUCHENNE trial are expected in early second quarter 2026. The company plans to share additional Phase I/II data at the Muscular Dystrophy Association annual meeting the following week and reiterated its intent to pursue a biologics license application using the accelerated approval pathway, with FDA engagement planned mid-year.

Pakola cited previously disclosed Phase I/II results, including an average 7.4-point functional improvement versus a CTAP model at 18 months, along with consistent microdystrophin expression. Most treated patients were 8 years and older, an age when functional decline is typically expected, according to management.

On safety, management reported no serious adverse events or adverse events of special interest in the Phase I/II study, including no thrombocytopenia or liver injury in 13 patients. Pakola attributed this profile to a proactive immune suppression regimen, a novel construct, and product purity with more than 80% full capsids, and said further safety detail is planned at the MDA meeting.

Responding to questions about FDA expectations for controlled data in DMD, Simpson said the pivotal protocol and statistical plan, which include comparisons to external controls, were prospectively reviewed by the agency and not altered mid-study. He stated that REGENXBIO does not view a placebo arm as ethical and that the confirmatory study was included in the original protocol.

Simpson said rapid confirmatory enrollment could increase RGX-202 safety exposure to about 50 patients at filing, versus 30 in the pivotal cohort. Top-line disclosures are expected to include safety data for all 30 pivotal patients and biomarker data for the primary endpoint, with around seven patients anticipated to have 12-month functional data at the time of release.

Management noted additional FDA interactions are planned before a pre-BLA meeting to align on analysis methods and data presentation, with the objective of de-risking the pre-BLA package. In Europe, the company is receiving feedback on designs that may include a placebo arm, though no start timeline was given.

REGENXBIO said its ophthalmology collaboration with AbbVie (ABBV) continues to advance RGX-314 in wet AMD and diabetic retinopathy (DR). For wet AMD, top-line pivotal data for subretinal delivery in the ATMOSPHERE and ASCENT studies are expected in the fourth quarter of 2026, which management described as part of the largest global gene therapy program in this indication.

Pakola referenced four-year durability data from a Phase I/II study and reported that in a fellow-eye bilateral dosing study, patients showed a 93% reduction in annualized anti-VEGF injection need at 12 months, with 60% remaining injection-free over that period.

For DR, site activation is underway for the pivotal Phase IIb/III NAVIGATE trial using suprachoroidal, in-office delivery of ABBV-RGX-314 at a 1e12 dose. First patient dosing is expected next quarter and would trigger a $100 million milestone payment from AbbVie. NAVIGATE’s Phase IIb portion is designed as a double-masked, sham-controlled trial enrolling 136 patients with non-proliferative DR, with a primary endpoint of at least a two-step improvement on the diabetic retinopathy severity scale at one year.

Phase II ALTITUDE data at dose level three showed no intraocular inflammation with a short course of prophylactic topical steroids, and 50% of patients achieved at least a two-step DRSS improvement without additional DR treatment. The company said it will retain flexibility to consider alternative endpoint approaches, including ordinal DRSS assessments, as data accrue.

REGENXBIO reported receiving a complete response letter for RGX-121 about two weeks before the call and clinical hold letters for both RGX-111 and RGX-121. Management said it believes the requirements to lift the holds are addressable and is preparing a CRL response while working toward a Type A meeting and a future BLA resubmission.

Pakola provided details on a serious adverse event in the RGX-111 study, noting that an independent third-party lab’s analysis of a resected tumor detected an AAV vector genome integration event associated with overexpression of the proto-oncogene PLAG1, with clonal integration into PLAG1 in tumor tissue. He said the findings were consistent with the hypothesis that integration at this site contributed to tumor formation, while also citing the patient’s prior stem cell transplant and chemotherapeutic exposure as background risk factors.

The report concluded that the patient’s neurocognitive development was above average, indicating mitigation of MPS I disease, and the analysis is expected to be published in a peer-reviewed journal this year. On biomarkers for Hunter syndrome, management said it tracks heparan sulfate and has assays available, and plans to include additional detail in its CRL response.

Chief Financial Officer Vithesh Taneja reported cash, cash equivalents, and marketable securities of $241 million as of December 31, 2025, compared with $245 million a year earlier. The balance reflected a $110 million upfront payment from Nippon Shinyaku and $145 million in net proceeds from a royalty monetization with HealthCare Royalty Partners, offset by operating cash use.

Research and development expense for 2025 was $228 million, up from $209 million in 2024, which management largely attributed to pivotal trial execution and manufacturing for RGX-202 and a program referred to as Sirvac. Total 2025 revenue was $170 million, including the Nippon Shinyaku upfront and increased royalties for Zolgensma and Evrysdi covered by the royalty monetization agreement.

Taneja said the company expects its year-end 2025 cash balance to fund operations into early 2027. This guidance excludes the anticipated $100 million AbbVie milestone on first dosing in NAVIGATE and any additional funds from the May 2025 HealthCare Royalty agreement, which could extend the runway into the second half of 2027. It also excludes any future revenue from the MPS programs.