The developer’s candidate for treating Duchenne muscular dystrophy (Duchenne) is RGX-202. The gene therapy is designed to deliver an optimized microdystrophin transgene with a unique C-terminal domain and a muscle specific promoter to support targeted therapy for improved resistance to muscle damage associated with Duchenne.
Ken Mills, CEO of Regenxbio, said the decision to delay dosing of patients, in a Phase 1/2 first in human clinical trial for RGX-202, was due to "an unexpected and isolated observation" in the final vial filling stage of the manufacturing process for clinical supply at a third-party contract manufacturer that did not meet the gene therapy company’s quality criteria.
“We’ve informed all key stakeholders and are investigating this situation. Based on this update, our current expectation is to be able to dose patients in the first half of 2023. Work preparing for trial initiation continues, including readying clinical trial sites, and manufacturing additional clinical supply,” he commented during an Q1 2022 earnings conference call on May 4.
The CEO said the event highlighted the importance of having in-house manufacturing capabilities. “I view this as a key to our longer-term success. While this will delay our current development plan, it certainly does not impact our strong commitment to developing RGX-202 for patients with Duchene.”
Mills also weighed on recent challenges for the US gene therapy industry. “Despite the recent market performance of the sector, I cannot help but be optimistic for the future of gene therapy. Over the years, we’ve seen a high level of investment in people, quality, and safety monitoring, and [there is] a deeper understanding of the science across the industry. The recent challenges experienced across the industry are not … uncommon for novel modalities like gene therapy. Challenges create opportunities in a relatively new field like gene therapy, [resulting in] greater collaboration and involvement with key leaders, including regulatory agencies.”
He said such collaboration should help the industry get gene therapies to patients with unmet needs as efficiently as possible.
New strategy
Mills said he believed the fundamentals of Regenxbio have never been stronger. “This is why we felt this past quarter was the right time to announce our 5 by 25 strategy to progress five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025.”
One of the leading candidates to meet that new strategy is RGX-314 for the treatment of wet AMD and diabetic retinopathy, and other chronic retinal diseases, said the CEO.
In September last year, the company announced a partnership with AbbVie to develop and commercialize RGX-314. Under the terms of the agreement, AbbVie will provide Regenxbio a US$370m upfront payment with the potential for the company to receive up to US$1.3bn in additional development, regulatory and commercial milestones.
“While the landscape for therapies being developed in both wet AMD and in diabetic retinopathy has changed over the past few months with some new product launches, and also high profile setbacks in the field, we believe the opportunity for RGX-314 has improved based on the encouraging endurance safety and efficacy data presented for both wet AMD and diabetic retinopathy. Overall, we plan to take full advantage of AbbVie’s leadership in eye care and its commercial strength as we work together to advance RGX-314.”
The 5 by 25 strategy is also expected to include RGX-202 along with RGX-121, for the treatment of Hunter syndrome, said Mills.
Beyond internal programs, the 5 by 25 strategy may also include therapies developed by its NAV technology licensees, added the CEO.
The company's NAV technology platform consists of over 100 novel adeno-associated virus (AAV) vectors, one of which was used in the US Food and Drug Administration (FDA) approved gene therapy, ZOLGENSMA, for spinal muscular atrophy in children under two years old. The developer has also licensed out its technology to a growing list of partners and licensees that includes Novartis, Eli Lily and Pfizer
“Our NAV technology platform is driving the field of AAV gene therapy forward with over 60 clinical trials utilizing NAV vectors registered in the National Institutes of Health (NIH) clinical trials database since 2015.
“With a number of additional AAV therapeutics being developed over a broad range of therapeutic areas and disease indications by our NAV technology licensees we believe these programs will also contribute key gene therapy products to meet our 5 by 25 strategy," noted Mills.