Lavengratinib shows early growth signal in phase 2 achondroplasia study

Preliminary phase 2 data suggest that oral lavengratinib (ABSK061), a selective fibroblast growth factor receptor (FGFR) 2/3 inhibitor, may increase growth velocity in children with achondroplasia, although findings are limited to 7 participants treated in the lowest-dose cohort of an ongoing open-label study.¹

At week 27, children receiving lavengratinib 0.064 mg/kg once daily had a mean increase in annualized height velocity (AHV) of 2.4 cm/year from baseline, according to Abbisko Therapeutics. All 7 met the sponsor-defined response threshold of at least a 25% improvement in AHV. “No serious adverse events or treatment discontinuations due to adverse events have been reported,” the company stated.¹ The results have not yet been reported in a peer-reviewed publication.

ABSK061-202 is a multicenter, open-label, dose-escalation phase 2 study enrolling children aged 3 to 12 years with achondroplasia. Participants are expected to receive once-daily oral lavengratinib for 78 weeks. The preliminary efficacy analysis included children aged 6 to 12 years who completed 27 weeks of treatment in the first and lowest-dose cohort.¹

Abbisko reported that preliminary safety evaluations have been completed for the first 3 dose cohorts, with participants in the higher-dose groups continuing treatment. No hyperphosphatemia or corneal toxicity—adverse effects associated with inhibition of other FGFR family members—had been observed at the data cutoff. However, the sponsor did not provide a complete adverse-event table, laboratory data, or participant-level efficacy findings.

Achondroplasia is most commonly caused by gain-of-function variants in FGFR3, resulting in impaired endochondral bone growth and disproportionate short stature. Beyond reduced linear growth, affected children may develop foramen magnum stenosis, spinal stenosis, sleep-disordered breathing, recurrent otitis media, and lower-extremity deformities. Clinical management therefore requires multidisciplinary surveillance rather than focusing exclusively on height.²

Vosoritide, a C-type natriuretic peptide analog administered by daily subcutaneous injection, is an established pharmacologic option for children with achondroplasia and open epiphyses.³ In a randomized phase 3 trial, vosoritide increased AHV by a placebo-adjusted 1.57 cm/year after 52 weeks.⁴ That result should not be directly compared with the lavengratinib finding because ABSK061-202 lacks a placebo group, uses change from each participant’s baseline, and currently has substantially shorter follow-up.

Lavengratinib takes a different approach by directly inhibiting FGFR3, along with FGFR2. The agent was designed to limit FGFR1 inhibition, which is associated with toxicities including hyperphosphatemia in the broader FGFR inhibitor class. The sponsor is developing a mini-tablet measuring less than 3 mm in diameter for administration with food or beverages.¹ Whether this formulation improves adherence relative to injectable therapy has not been evaluated.

The FDA has granted lavengratinib Rare Pediatric Disease and Orphan Drug designations for achondroplasia, but these designations do not constitute approval or establish efficacy.¹ The drug remains investigational, and the reported findings do not support conclusions about final adult height, body proportionality, functional outcomes, or effects on achondroplasia-related complications.

Interpretation is further constrained by the 7-patient sample, open-label design, absence of a concurrent control group, and reliance on annualized growth calculated from 27 weeks of observation. Growth velocity can vary by age, pubertal status, and baseline measurement interval. Longer follow-up will also be needed to characterize potential skeletal, ocular, metabolic, and growth-plate effects of sustained FGFR2/3 inhibition. Abbisko expects 6-month results from additional dose cohorts by the end of 2026.¹

References

1. Abbisko Therapeutics. Abbisko Therapeutics announces positive preliminary phase 2 results with lavengratinib (ABSK061) for the treatment of achondroplasia. Published September 21, 2026. https://www.prnewswire.com/news-releases/abbisko-therapeutics-announces-positive-preliminary-phase-2-results-with-lavengratinib-absk061-for-the-treatment-of-achondroplasia-302881858.html

2. Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007;370(9582):162-172.

3. BioMarin Pharmaceutical Inc. VOXZOGO (Vosoritide) for Injection, for Subcutaneous Use: Prescribing Information. Revised October 2023.

4. Savarirayan R, Tofts L, Irving M, et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet. 2020;396(10252):684-692.