The resubmission for RGX-121, expected in the third quarter, comes as the FDA has deemed REGENXBIO’s existing data “sufficient” to support an accelerated filing. It immediately follows a similar reversal of position regarding uniQure’s embattled Huntington’s disease gene therapy.
Step right up, the FDA’s regulatory reversal train is boarding, making U-turns for biotechs with recently rejected or delayed rare disease therapies. REGENXBIO—whose Hunter syndrome gene therapy was turned away by the agency in February—will resubmit for approval in the third quarter.
In its complete response letter for RGX-121, the FDA cited “uncertainty” over the eligibility criteria that REGENXBIO used in its registrational study and the biotech’s use of external controls, which it said “lack the comparability” with trial participants. The FDA recommended the company use “an appropriate untreated control.”
Now, the agency has “acknowledged the existing NAVSUNLI [RGX-121] clinical data is sufficient to be considered for the accelerated approval pathway and that the Company does not need to enroll additional patients or conduct additional studies, including the FDA’s previously recommended incorporation of an untreated control arm,” REGENXBIO announced on Monday, using an apparently new moniker for the gene therapy.
REGENXBIO shares were trading up nearly 12% when the market opened on Monday.
This latest FDA 180-degree turn comes after a “recent collaborative discussion” that occurred as part of REGENXBIO’s appeal of the February rejection.
The agency has also asked that REGENXBIO request a Type A meeting to review existing longer-term biomarker and clinical data, according to the company’s press release, following which the FDA said it should submit a new biologics license application. The agency said it would review a resubmission on an “expedited basis, with labeling discussions to begin shortly following the resubmission.”
REGENXBIO expects this meeting to take place in July.
“We are encouraged by recent signals from the new FDA leadership reinforcing a commitment to address the unique nature of rare diseases and use the accelerated approval pathway to bring transformative therapies to patients with serious, unmet medical needs,” REGENXBIO CEO Curran Simpson said in a prepared statement on Monday. “We will continue to work closely with the FDA and remain focused on bringing this important therapy to boys living with Hunter syndrome as quickly as possible.”
REGENXBIO’s resubmission for RGX-121 will likely join a first submission in the third quarter for uniQure’s embattled Huntington’s disease gene therapy. Last week, the FDA agreed that three-year data from the company’s Phase 1/2 trial were sufficient to support an accelerated BLA.
This decision reversed the call of Marty Makary’s FDA to require a sham-controlled Phase 3 trial before it would consider AMT-130 for approval. Notably, that request was a reversal of the guidance given to uniQure by the agency in 2024.
These latest moves punctuate an emerging trend toward an FDA more flexible toward rare disease in its current “caretaker mode” under acting FDA commissioner Kyle Diamantas. Diamantas met earlier this month with rare disease groups, reportedly to mend fences with a sector that has faced a much more stringent FDA of late.
The REGENXBIO and uniQure decisions also suggest the agency’s intent to back up its recent guidance that cell and gene therapy developers should leverage innovative clinical trial designs, including externally-controlled trials—those using historical or real-world data (RWD).
UniQure’s pivotal Phase 1/2 trial—which returned positive 3-year data in September 2025—compared the clinical outcomes for 24 patients given AMT-130 to a propensity score-matched external control from the Enroll-HD natural history data set.
Other rare disease drug developers have reported positive news of late, including Disc Medicine, which has reached an agreement with the FDA to resubmit a new drug application for its recently rejected rare blood disease drug, and Replimune, which said last month that it would resubmit its biologics license application for its rebuffed melanoma therapy “in the coming days.” Replimune’s announcement came roughly two weeks after Makary was forced out.
