RiboX's RXRG001 becomes first circular RNA drug with published human trial results

RiboX Therapeutics' RXRG001 is the first circular RNA drug to report published human trial results. The New England Journal of Medicine carried initial SPRINX-1 findings showing the therapy increased saliva production in six patients with radiation-induced xerostomia, Inside Precision Medicine reported.

Three patients received 4 micrograms of RXRG001 and three received 10 micrograms, each as a single infusion into a single parotid gland. All six had experienced chronic xerostomia for at least two years after radiation treatment for head and neck cancer. No dose-limiting toxic effects were observed during at least 120 days of follow-up, and treatment-related adverse events were transient and limited to grade 1 or 2, including low-grade fever, fatigue and chills. The trial had no control group and limited follow-up.

What the drug does

RXRG001 carries circular RNA encoding aquaporin-1, a water channel protein of cell membranes, inside a lipid nanoparticle. It is delivered directly into the parotid gland, the major salivary gland responsible for thin, watery saliva, in a procedure that takes under 10 minutes. Circular RNA forms a covalently closed loop that resists degradation and, in theory, supports sustained protein production. Earlier clinical studies showed viral vectors carrying the AQP1 gene can increase water transport in salivary epithelial cells.

Radiation therapy for head and neck cancer often damages salivary glands, reducing saliva secretion and causing dry mouth, difficulty chewing and swallowing, impaired oral health and diminished quality of life. RiboX says there is a significant unmet medical need for new treatments. In animals, a single dose of RXRG001 raised salivary flow for about four weeks. RiboX dosed the first SPRINX-1 patient in the week before 9 March 2025.

One patient's response

One patient had lived with the condition for 17 years, to the point where eating, swallowing and speaking had become difficult and at times dangerous. A few weeks after dosing, his saliva came back; later, eating a cookie, he swallowed without water for the first time in years. Henry T. Hoffman, an otolaryngologist at University of Iowa Health Care Medical Center, led the trial, which measured unstimulated and stimulated saliva production alongside patient-reported assessments.

Weiyi Zhang, RiboX's chief executive, told Inside Precision Medicine that the clinical numbers do not capture what changed for patients. "When we look at the paper and those numbers, it's kind of cold because we don't know how those numbers change patients' lives," Zhang said.

What is still open

Investigators are still assessing dose-response relationships, duration of effect and longer-term safety at higher dose levels. Enrollment in the ongoing study continues. The paper offers early clinical proof of concept, but questions remain about the durability, consistency and safety of the response.