Regenxbio: ‘CDMO issue validates inhouse gene therapy investment’

Regenxbio will begin inhouse production of material for its Duchenne Muscular Dystrophy (DMD) gene therapy after a quality issue at a third-party manufacturer delayed clinical trial dosing.

The initiation of dosing adeno-associated viral (AAV) based gene therapy candidate RGX-202 for a Phase I/II clinical trial has been delayed by between six and 12 months, Regenxbio announced last week during its first quarter 2022 financial results.

According to CEO Ken Mills, the delay is due to an issue at an undisclosed contract development and manufacturing organization (CDMO).

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“We had this unexpected, isolated observation in the very final stages of a manufacturing process for RGX-202 clinical supply,” he told stakeholders. “The unexpected nature of this in the late stage caused us to have to report this delay and re-guide first patient dose to the first half of 2023 which is, I think, telegraphing that we have a 6-to-12-month delay. This was something that was reported at a third-party contract manufacturer of ours and that didn’t meet our quality criteria.”

While clearly a disappointment to Regenxbio and the DMD community, the incident has highlighted “the importance of our inhouse GMP manufacturing facility,” he continued, adding it reinforces the message Regenxbio has been pushing over the past few years and the investment it has made in its own operations.

The firm first announced it was building an adeno-associated viral (AAV) vector facility in 2019 within its 132,000 square-foot headquarters in Rockville, Maryland. At the time, the firm said the plant would ensure manufacturing capacity availability within an industry where the AAV supply-demand balance is uneven, but the quality issue at the unnamed CDMO has demonstrated the importance for Regenexbio of controlling its manufacturing network.

“We’ve been looking at the landscape for a while, we’ve been communicating with all of you about how important we think it is to bring the quality and availability of clinical supply and commercial supply for our pipeline in house,” Mills said last week

Operations begin

“We started that investment, pre-COVID, with the build out of our headquarter facility in the intent to bring online the GMP facility,” he continued, adding the plant is now open.

“Our internal GMP capability is operational, supporting the high yield manufacture of quality AAV therapeutics across a diverse range of programs and at the scales necessary to support clinical development and commercialization,” he said.

The 21,000 square-foot plant includes a pilot plant, advanced analytics lab, multiple 2,000 liter bioreactor suites for GMP manufacturing of both drugs, and fill-finished capabilities to support multiple programs.

“We plan for the first runs in this facility to support our clinical supply for RGX-202, and RGX-314 program.” RGX-314 is being developed as a novel, one-time subretinal treatment that includes the NAV AAV8 vector containing a gene encoding for a monoclonal antibody fragment for wet age-related macular degeneration (AMD).

“We’re also able to begin to install new process improvements that we plan to use in our facility that will be expected to produce, for example, in the case of RGX-202 approximately five times improvements in vector yield per batch than previously used processes.”