Safety concerns spur FDA to again halt testing of Regenxbio gene therapy

Dive Brief:

The Food and Drug Administration has placed another clinical hold on a Regenxbio gene therapy after study investigators detected abnormalities on the MRIs of five trial participants.
The company said Monday that masses that are “likely” benign were found in patients who received the treatment, RGX-121, about three to six years ago for a condition known as Hunter syndrome. Those patients did not exhibit any symptoms and “continue to do well clinically and have demonstrated overall stability to improvement on neurocognitive and neurobehavioral assessments,” Regenxbio said.
Still, the announcement represents the latest regulatory setback for RGX-121 this year. The FDA put testing on pause in January due to other safety worries and rejected Regenxbio’s application a month later. Regenxbio had been preparing a new submission after aligning with regulators, but now no longer plans to file that application in “the near term,” the company said Monday. Shares plunged more than 25% in early Monday trading.

Dive Insight:

The clinical hold announced Monday adds another twist to what’s already been a tumultuous development journey for Regenxbio.

RGX-121 is designed to be a one-time treatment for Hunter syndrome, a genetic disorder that disrupts the body’s ability to break down sugar molecules. Clinical trials showed the drug’s potential to reduce markers of disease activity. But testing was stopped in January when a participant receiving a similar treatment for a different rare condition developed brain cancer. The agency then delayed an approval decision by three months and eventually turned back Regenxbio’s application, as staff reviewers found the company’s “surrogate” trial endpoint unconvincing.

Regenxbio appealed the decision and requested an urgent “Type A” meeting between to review the results. That meeting led to an agreement on what it’d take for Regenxbio to win an accelerated approval — a speedier-than-normal clearance based on a thinner body of evidence. Regenxbio announced plans to resubmit an application in June.

Now, the therapy’s future is unclear. Regenxbio stressed in its statement that there is “no clinical or pathological evidence to confirm the nature or causation of the spine MRI findings,” and that no brain masses or nodules were identified either. The company also noted that, because spine MRIs aren’t normally conducted on Hunter syndrome patients, the “underlying prevalence and clinical significance of these types of asymptomatic findings” are “unknown.”

Regenxbio and partner NS Pharma are evaluating data and will incorporate the findings, as well as feedback from the FDA, into their future development strategy.