RIBOMIC Inc. has announced positive results from the Phase 2 Cohort 2 trial of umedaptanib pegol, an anti-FGF2 aptamer therapeutic, in pediatric patients aged 5-14 with achondroplasia. The high-dose biweekly administration group demonstrated significant improvements in height growth rates, with some patients achieving increases of up to 5.0 cm/year.
Phase 2 Trial Design and Results
The Phase 2 clinical trial evaluated two dosing regimens of umedaptanib pegol, both delivering the same total dose but with different administration schedules. Cohort 1 received weekly subcutaneous injections of 0.3 mg/kg, while Cohort 2 received biweekly injections of 0.6 mg/kg over a 34-week treatment period.
In Cohort 2, all six subjects completed the trial, with five showing increased height growth rates. Two subjects demonstrated particularly significant improvements of +5.0 cm/year and +2.0 cm/year. Combined with results from Cohort 1, where two subjects achieved growth rates of +4.6 cm/year and +3.3 cm/year, four patients with markedly increased height growth exceeded the average height growth rate of +1.7 cm/year reported for Voxzogo (vosoritide), the currently approved achondroplasia treatment manufactured by BioMarin.
The mean height growth rates for both cohorts were comparable to Voxzogo, with Cohort 1 achieving +1.5 cm/year and Cohort 2 achieving +1.4 cm/year. No safety concerns arose throughout the Phase 2 clinical trial, establishing proof-of-concept for umedaptanib pegol as an achondroplasia treatment.
Therapeutic Advantage and Patient Benefits
The study demonstrated that increasing the total dose allows for extending the dosing interval, potentially offering significant advantages for pediatric patients who require long-term treatment. Umedaptanib pegol is expected to achieve results comparable to Voxzogo with biweekly or weekly dosing, compared to Voxzogo's daily subcutaneous administration requirement.
Phase 3 Development Plans
Based on the successful Phase 2 completion, RIBOMIC is planning a Phase 3 clinical trial to further verify umedaptanib pegol's efficacy. Previous nonclinical studies using achondroplasia animal models demonstrated that bone elongation rates increased proportionally with drug dose, supporting the rationale for dose escalation.
The Phase 3 trial will increase the weekly subcutaneous dose to approximately 1 mg/kg and include younger pediatric patients around two years of age. This approach is expected to yield significantly improved treatment outcomes compared to currently approved drugs.
The Phase 3 trial is scheduled to begin in the first quarter of fiscal year 2026 and conclude within fiscal year 2027. RIBOMIC aims to obtain regulatory approval by the end of fiscal year 2028, utilizing preferential measures associated with the drug's orphan drug designation from Japan's Ministry of Health, Labor and Welfare.
About Umedaptanib Pegol and Achondroplasia
Umedaptanib pegol is a novel oligonucleotide-based aptamer, formerly designated RBM-007, with potent anti-FGF2 (fibroblast growth factor 2) activity. The drug has received orphan drug designation from Japan's Ministry of Health, Labour and Welfare.
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which makes FGFR3 more easily activated. This leads to excessive influx of FGF signals, inhibiting normal cartilage and tissue development, resulting in short stature with limb shortening. The rare disease affects approximately 1 in 25,000 newborns and is designated as an intractable disease, creating urgent need for effective new treatments.
