RiboX's Circular RNA Therapy RXRG001 Cleared for Phase 1/2a Trial in Radiation-Induced Xerostomia and Hyposalivation
RiboX stated that this is the first IND clearance the FDA has granted for any circular RNA therapy.
RiboX Therapeutics has received clearance of an IND application from the FDA for RXRG001, an investigational circular RNA therapy, enabling a phase 1/2a clinical trial that the company will refer to as the SPRINX-1 Study, in patients with radiation-induced-xerostomia (RIX) and hyposalivation.1
Notably, RiboX stated that this is the first IND clearance the FDA has granted for any circular RNA therapy. The company noted that RIX and hyposalivation are common adverse effects produced in patients who have undergone radiation therapy for head and neck cancers (HNC).
"RIX is a devastating life-long health issue for patients with HNC,” Yizhen Xu, MD, PhD, the chief medical officer of RiboX, said in a statement.1 “Although radiation therapy improves patients' survival, its damage to the salivary glands leads to an impaired quality of life of many cancer survivors. RXRG001 may offer a potential effective and sustained therapeutic option for RIX patients. We are excited to conduct clinical trials to further evaluate its efficacy and safety in patients."
Specifically, RXRG001 is a lipid nanoparticle containing circular mRNA that codes for the water channel protein human aquaporin 1 (hAQP1). It is intended to produce overexpression of hAQP1 in order to promote elevated saliva production to ameliorate the symptoms of dry mouth associated with RIX. RiboX pointed out that in an animal model the RNA therapy significantly increased salivary flow for about 4 weeks after a single dose.
"The FDA's clearance of the IND application for RXRG001 is an acknowledgment of our innovative capabilities, robust technology, and competitiveness in the field of circular RNA therapeutics," Weiyi Zhang, PhD, the chief executive officer of RiboX, added to the statement.1 "RiboX will advance the clinical development of RXRG001, continue leveraging the unique advantages of circular RNA technology in therapeutic applications, and introduce more pioneering treatments to patients around the world."
According to RiboX Therapeutics, circular RNAs, which are naturally produced at low levels in animal cells, are able to be engineered for therapeutic purposes by means of in vitro transcription and circularization.2 The company lists several potential advantages of circular RNA approaches to treatment of disease, including “improved stability, tunable expression, convenient manufacturing, and low immunogenicity.”
RXRG001 is not the only advanced therapeutic that companies have attempted to apply to the treatment of xerostomia. MeiraGTx’s AAV2-hAQP1, an investigational gene therapy intended to treat grade 2/3 radiation-induced xerostomia (RIX), has previously demonstrated clinically meaningful improvements in grade 2/3 xerostomia symptoms in participants treated in the now-completed phase 1 AQUAx clinical trial (NCT04043104).3 Data announced in June 2023 from all 24 participants having reached 12 months of follow-up showed that both unilateral (n = 8; 66%) and bilateral (n = 10; 83%) cohorts reported improvements on the Global Rate of Change Questionnaire (GRCQ) compared with baseline. The responders reported changes of at least 2 in symptoms they considered “important” or “very important” and 5 in the bilateral cohort and 4 in the unilateral cohort gave the highest improvement scores (6 or 7) in xerostomia symptoms. A phase 2 clinical trial (NCT05926765) for AAV2-hAQP1 is currently underway.
On the other hand, an adipose-derived mesenchymal stem/stromal cell (ASC) therapy did not significantly improve xerostomia in patients with previous head and neck cancer compared with placebo, according to results of a single-center, phase 2, randomized trial (NCT04776538) that were announced in an online paper for the American Association for Cancer Research (AACR) Annual Meeting 2024, held on April 5-10, 2024, in San Diego, California.4 First author Kathrine Kronberg Jakobsen, MD, PhD, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital- Rigshospitalet, and Section for Biostatistics and Evidence-Based Research, the Parker Institute, Copenhagen University Hospital- Bispebjerg and Frederiksberg, Denmark, and colleagues assessed 120 patients with previous head and neck cancer that received ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands.
“We could not confirm superiority of the ASC relative to placebo,” Jakobsen and colleagues wrote.4 “ASC therapy significantly improved UWS in previous patients with head and neck cancer, whereas placebo resulted in an insignificant increase.”
