Abbisko's FGFR2/3 Inhibitor Lavengratinib Lifts Height Velocity in Phase 2 Achondroplasia Cohort
核心洞察
Abbisko Therapeutics (搜索) reported preliminary Phase 2 results for lavengratinib (搜索) (ABSK061) in children with achondroplasia (搜索), showing a mean +2.4 cm/year gain in annualized height velocity at Week 27.
All seven participants aged 6 to 12 years in the lowest dose cohort of 0.064 mg/kg once daily met the responder threshold of at least 25% improvement in annualized height velocity.
No serious adverse events, treatment discontinuations, or FGFR1 (搜索)/FGFR2 (搜索)-associated toxicities such as hyperphosphatemia and corneal toxicity were observed in the first three dose cohorts.
Abbisko Therapeutics (搜索) has reported positive preliminary efficacy results from the Phase 2 ABSK061-202 study of lavengratinib (搜索) (ABSK061), an orally available selective small-molecule FGFR2 (搜索)/3 inhibitor, in children with achondroplasia (搜索). In the first and lowest dose cohort, seven participants aged 6 to 12 years who received 0.064 mg/kg once daily for 27 weeks achieved a mean increase of +2.4 cm/year in annualized height velocity (AHV) from baseline, with a 100% responder rate.
A responder in the study is defined as a participant achieving at least a 25% improvement in AHV from baseline. All seven participants in cohort 1 have completed six months of treatment. Participants enrolled in higher dose cohorts are continuing treatment.
Trial Design and Dosing
ABSK061-202 is a Phase 2, multicenter, open-label, dose-escalation study evaluating the safety and efficacy of lavengratinib (搜索) administered once daily by the oral route in children aged 3 to 12 years with achondroplasia (搜索). All participants are planned to receive treatment for 78 weeks.
The study has completed the preliminary safety evaluation of the first three dose cohorts, with no safety concerns identified to date. Six-month efficacy and safety results are expected by the end of 2026.
Safety Profile
Abbisko reported that overall safety and tolerability were favorable. To date, no serious adverse events or treatment discontinuations due to adverse events have been reported. No specific safety risks associated with FGFR pathway inhibition have been observed, including FGFR1 (搜索) or FGFR2 (搜索)-associated adverse events such as hyperphosphatemia and corneal toxicity.
The absence of FGFR1 (搜索)-associated toxicity is central to the compound's design rationale. First-generation pan-FGFR inhibitors demonstrated clinical efficacy in multiple tumors carrying FGFR2 (搜索)/3 variants and have steadily gained regulatory approval globally, but their therapeutic window and clinical efficacy have been limited by side effects associated with FGFR1 inhibition. Lavengratinib (搜索) was designed to reduce FGFR1 activity while maintaining potency against FGFR2 and FGFR3 (搜索), which Abbisko expects to translate into a wider therapeutic window and improved clinical efficacy as a new-generation FGFR inhibitor.
Pediatric Formulation
Lavengratinib (搜索) uses a mini-tablet formulation developed by Abbisko, with each tablet less than 3 mm in diameter compared with conventional tablets of roughly 8 to 10 mm. The company states that the smaller tablets allow for easier administration in children and can be given with food and drink.
Regulatory Status
Lavengratinib (搜索) is a novel, orally bioavailable, highly potent and selective small-molecule inhibitor of FGFR2 (搜索) and FGFR3 (搜索) that was independently discovered and is wholly owned by Abbisko Therapeutics (搜索). According to the company, it is the first FGFR2/3 inhibitor to enter clinical trials globally. For the treatment of achondroplasia (搜索), lavengratinib has received both Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (搜索), and its Phase 2 clinical trial is ongoing.