FDA grants rare pediatric disease designation to YOLT-203 for primary hyperoxaluria type 1

The FDA has awarded a rare pediatric disease designation to the in vivo gene editing therapy YOLT-203 for the potential treatment of patients with primary hyperoxaluria type 1 (PH1), YolTech Therapeutics, the developer of the therapy, announced in a news release.¹

Completion of the phase 1 study of YOLT-203 is expected for January 2026.

A rare pediatric disease designation is granted to drugs and biologics that are intended to treat diseases that affect fewer than 200,000 patients and pose a serious life-threatening risk to children under the age of 18. Under the designation, YOLT-203 is eligible to receive a priority review voucher following a potential FDA approval of the therapy. This voucher can be used to expedite the review of another drug or sold to another company.

According to YolTech, YOLT-203 is encapsulated within lipid nanoparticles, which are recognized and internalized by liver cells upon intravenous administration. The company explained, “Once inside, the YolCas12 editor protein, guided by the corresponding guide RNA (gRNA), targets and corrects mutations in the AGXT gene, aiming to reduce harmful oxalate levels in the blood, thereby offering a potential one-time, curative treatment for PH1.”¹

YOLT-203 is currently being assessed in the early phase 1 YOLT-203-101 trial (NCT06511349), which is evaluating the safety and tolerability of the therapy in adult and pediatric patients with PH1. The study will also assess the effects of a single administration of the gene editing therapy on plasma oxalate levels.

According to the news release, YOLT-203 is the first in vivo gene editing therapy developed specifically for PH1, as well as the first in vivo gene editing therapy to enter into clinical trials globally for a rare pediatric disease.

In total, the single-arm, open-label YOLT-203-101 trial plans to enroll 7 patients with PH1 through a single center in China. The launch of the trial was officially announced last month, with the first adult patient in the study having been dosed on August 5, 2024, and the first pediatric patient having been dosed on August 20, 2024.²

To be eligible for enrollment, patients need to be 2 years of age or older, have a diagnosis of PH1, harbor AGXT gene mutations, and have at least 2 instances of 24-hour urinary oxalate levels of 0.7 mmol/1.73m2 or greater per day or the ratio of urinary oxalate to creatinine in a single urine collection must be higher than the upper limit of normal for the patients’ age group. Additionally, if patients are treated with vitamin B6, the treatment must be stable for 90 days before enrollment and remain stable for the duration of the study.³

The dose escalation phase of the trial will involve 3 dose level groups that will be dosed using an accelerated titration approach. Patients will be followed for 52 weeks.

The primary end point for the trial is safety and tolerability, measured by the incidence and severity of adverse events (AEs) and serious AEs through week 52. Secondary end points include various pharmacokinetic measures, such as the peak plasma concentration through day 14, as well as various pharmacodynamic measures, such as changes in eGFR at various time points.

Completion of the phase 1 study is expected for January 2026. Following the 1-year main study, the sustained safety and efficacy of the treatment will continue to be monitored in patients for up to 15 years.

References

1. YolTech Therapeutics receives U.S. FDA Rare Pediatric Disease Designation for YOLT-203 in treating primary hyperoxaluria type 1. News release. YolTech Therapeutics. Published online and accessed September 4, 2024. https://www.prnewswire.com/news-releases/yoltech-therapeutics-receives-us-fda-rare-pediatric-disease-designation-for-yolt-203-in-treating-primary-hyperoxaluria-type-1-302237915.html

2. YolTech Therapeutics administers first patient dose in IIT of YOLT-203, the world's first in vivo gene editing therapy for PH1. News release. YolTech Therapeutics. August 22, 2024. Accessed September 4, 2024. https://www.prnewswire.com/news-releases/yoltech-therapeutics-administers-first-patient-dose-in-iit-of-yolt-203-the-worlds-first-in-vivo-gene-editing-therapy-for-ph1-302228388.html

3. Clinical exploration study of YOLT-203 in the treatment of type 1 primary hyperoxaluria (PH1). ClinicalTrials.gov. Last updated August 21, 2024. Accessed September 4, 2024. https://clinicaltrials.gov/study/NCT06511349