FDA Grants Rare Pediatric Disease Designation to EXG-34217 for Dyskeratosis Congenita

Author(s):

Ashley Gallagher, Associate Editor

Treatment is typically tailored to the individuals, with HCT being the only curative treatment bone marrow failure, but long-term outcomes are generally poorer due to toxicities.

The FDA granted rare pediatric disease designation (RPDD) to EXG-34217 (Elixirgen Therapeutics, Inc.) for the treatment of dyskeratosis congenita and related telomere biology disorders (DC/TBD). EXG-34217 is made of autologous CD34+ hematopoietic stem cells (HCT), which were treated ex vivo with EXG-001, according to the news release.¹

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“We’re pleased with the FDA’s decision to grant EXG-34217 RPDD for the treatment of DC/TBD, a rare group of diseases that result in abnormally short telomeres that can lead to bone marrow failure and other serious health conditions,” Aki Ko, CEO of Elixirgen Therapeutics, said in a news release. “The RPDD is a recognition of the significant unmet need in this space and the potential of EXG-34217, and we look forward to working with the FDA as we continue to advance this program.”¹

DC/TBD are telomere biological disorders which can cause dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, according to the National Library of Medicine. The condition can also increase the risk of progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors, and pulmonary fibrosis. Treatment is typically tailored to the individuals, with HCT being the only curative treatment for BMF and leukemia. However, the long-term outcomes are generally poorer due to treatment toxicities. Therefore, newer treatment options are needed for the disease.²

Currently, investigators are enrolling individuals from the Cincinnati Children’s Hospital Medical Center for a phase 1/2 trial (NCT04211714), and there is 1 completed phase 1/2 clinical trial (NCT04863131). In the phase 1/2 trial, investigators found that there was successful ex vivo telomere elongation with EXG-34217. It increased the length of telomere by 1.24-fold, which brought them into the healthy control range. Furthermore, there were no acute or long-term adverse events observed for up to 9 months.³

About The Trial

Trial Name: Study to Evaluate of EXG34217 in Patients With Telomere Biology Disorders With Bone Marrow Failure

ClinicalTrials.gov ID: NCT04211714

Sponsor: Elixirgen Therapeutics Inc

Completion Date (Estimated): April 2027

In the study, investigators included patients 12 years or older with mild or moderate BMF and a diagnosis of telomere biology disorders. The primary end points included the number of AEs, change in physical examination, change in electrocardiography, change in clinical laboratory evaluations, and change in immunogenicity. Secondary end points included the change in telomere length and improvement of blood counts, according to the clinical trial information.⁴

“The encouraging data in this study represent the first time that ex vivo telomere elongation of CD34+ cells has been demonstrated in a patient with TBD. Dyskeratosis congenita has historically been characterized by a triad of abnormalities in the skin, nails and oral mucosa but can also include pulmonary and liver disease,” Kasiani C. Myers, MD, associate professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center, said in a news release. “The data presented here provide promising early signs of the potential of EXG-34217 to provide an alternative treatment option for bone marrow failure in these patients and their families.”³

REFERENCES

1. Elixirgen Therapeutics Receives Rare Pediatric Disease Designation for EXG-34217 in Dyskeratosis Congenita and Related Telomere Biology Disorders. News release. September 25, 2024. Accessed September 25, 2024. https://www.globenewswire.com/news-release/2024/09/25/2952915/0/en/Elixirgen-Therapeutics-Receives-Rare-Pediatric-Disease-Designation-for-EXG-34217-in-Dyskeratosis-Congenita-and-Related-Telomere-Biology-Disorders.html

2. Savage SA, Niewisch MR. Dyskeratosis Congenita and Related Telomere Biology Disorders. 2009 Nov 12 [Updated 2023 Jan 19]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. https://www.ncbi.nlm.nih.gov/books/NBK22301/

3. Elixirgen Therapeutics Presents New Clinical Data Demonstrating Ex Vivo Telomere Elongation with EXG-34217 in Dyskeratosis Congenita at the 64th ASH Annual Meeting. News release. December 12, 2022. Accessed September 25, 2024. https://elixirgentx.com/press-releases/elixirgen-therapeutics-presents-new-clinical-data-demonstrating-ex-vivo-telomere-elongation-with-exg-34217-in-dyskeratosis-congenita-at-the-64th-ash-annual-meeting/

4. Safety and Immunogenicity of EXG-5003. ClinicalTrials.gov identification: NCT04863131. Updated January 26, 2023. Accessed September 25, 2024. https://clinicaltrials.gov/study/NCT04863131