REGENXBIO Inc. (RGNX) shares fell 25% to $8.05 on Monday after the U.S. Food and Drug Administration placed a clinical hold on RGX-121, the company's investigational gene therapy for Hunter syndrome — an order that pauses an ongoing trial or delays a planned one while the agency reviews a program. Trading in the stock was briefly halted ahead of the announcement.

The hold followed results from an expanded MRI monitoring program, which turned up asymptomatic findings in five patients. Each patient had a small nodule or cystic mass on the spine, and all five had received injections of RGX-121 roughly three to six years earlier. The findings were detected through imaging alone, with no symptoms reported. Extended surveillance of this kind is a fixture of gene-therapy development: FDA guidance recommends long-term follow-up of gene-therapy patients for as long as 15 years after dosing, because relevant effects can take years to surface.

Researchers classified the findings as non-serious. Radiologists assessed them as likely benign, and there is no clinical or pathological evidence linking them directly to the therapy. Even so, the FDA moved to place the program on clinical hold, and Regenxbio said it no longer expects to resubmit its Biologics License Application (BLA) for RGX-121 in the near term.

The decision is a reversal from earlier guidance. As recently as June, the FDA had told Regenxbio that no additional studies were needed before resubmitting the BLA in the third quarter. That timeline is now off the table.

Second Hold in Recent Months

It is the second Regenxbio program to be paused by the FDA in recent months. RGX-111, a candidate for MPS I — also known as Hurler syndrome, a related lysosomal storage disorder — was placed on clinical hold earlier this year, just weeks before a key approval decision. At the time, the hold was extended to RGX-121 because of similarities between the two therapies.

What the CEO Said

Chief Executive Officer Curran Simpson said the findings appear “unique and limited” to the Hunter syndrome program, but acknowledged that they “require longer-term follow-up and additional data analysis” before the company can fully assess the benefit-risk profile of RGX-121.

All five patients continue to show overall stability or improvement on neurocognitive and neurobehavioral assessments.

Hunter syndrome, also known as mucopolysaccharidosis II (MPS II), is a rare genetic disorder in which the body cannot break down complex sugar molecules because it lacks the enzyme iduronate-2-sulfatase. The condition, estimated to affect roughly one in 100,000 to 170,000 male births, mostly affects boys and is life-limiting, with patients typically surviving into their 20s. Approved enzyme replacement therapy can ease some symptoms but does not cross the blood-brain barrier, leaving the neurocognitive decline that RGX-121 — which delivers a working copy of the gene directly into the central nervous system — is designed to counter.

Other Programs Still on Track

Regenxbio said its Duchenne muscular dystrophy and wet age-related macular degeneration (AMD) programs are not affected by the hold, noting that they use a different capsid and different routes of administration.

The company still plans to submit a BLA for its Duchenne candidate, RGX-202, in the current quarter. Topline data for its wet AMD candidate, RGX-314, co-developed with AbbVie, is expected in the fourth quarter, a readout that analysts have flagged as a key stock catalyst for Regenxbio.

News of the hold was also felt among companies in adjacent spaces: Sarepta Therapeutics, which markets the approved Duchenne gene therapy Elevidys, fell 3.3%, and EyePoint, a developer of treatments for retinal diseases, dropped 4.3% on the day.

Earlier this month, Barclays analyst Eliana Merle downgraded Regenxbio to Equal Weight from Overweight, citing an unclear regulatory environment and rising competition as risks to both programs.

Regenxbio said it is working with partner NS Pharma, the U.S. arm of Japan's Nippon Shinyaku, to evaluate additional patient imaging and longer-term follow-up data, and will incorporate FDA feedback into its next steps for RGX-121. Clinical holds are resolved case by case — companies typically submit requested data or protocol changes, and the FDA then decides whether to lift the order, with no fixed timeline.

Source: CoinCentral