Investigational oral therapy performs similarly to human GH in pediatric GH deficiency
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Key takeaways:
- Children receiving 1.6 mg/kg daily ibutamoren had an annualized height velocity increase of 8 cm per year at 1 year.
- The height velocity increase is similar to reference groups receiving recombinant human GH.
An oral medication that stimulates the growth hormone secretagogue receptor 1a induced height velocity increases similar to those seen with recombinant human GH for children with pediatric GH deficiency, according to trial data.
In findings from the OraGrowtH210 trial presented at the Pediatric Endocrine Society meeting, children receiving ibutamoren (LUM-201, Lumos Pharma) had increases in annualized height velocity of up to 8 cm per year. Combined long-term data from OraGrowtH210 and the OraGrowtH212 phase 2 trial revealed children receiving ibutamoren had less of a decline in height velocity from 1 year to 2 years than a reference group receiving human GH. The findings showed ibutamoren may give children with GH deficiency an alternative treatment option to injectable human GH in the future, according to Andrew Dauber, MD, MMSc, chief of endocrinology at Children’s National Hospital in Washington, D.C.
“Right now, there’s no oral option for patients, the only options are injections,” Dauber told Healio. “There are weekly injections available, but it’s still an injection and there’s still patients who are just not interested or really scared of it. ... I think if there was an oral option for these patients with mild GH deficiency, lots of patients would be interested.”
The OraGrowtH210 trial is a phase 2 dose-finding study in which 81 children with moderate pediatric GH deficiency were randomly assigned to 0.8 mg/kg, 1.6 mg/kg or 3.2 mg/kg ibutamoren or 34 µg/kg recombinant human GH once daily for 2 years. All participants were treatment naive, had a height standard deviation score of –2 or less and had delayed bone age. Annualized height velocity and insulin-like growth factor I levels were collected at 6 months and 1 year.
“[Ibutamoren] is a pill that’s stimulating the body’s own GH,” Dauber said in describing the difference between the oral medication and recombinant human GH. “It’s telling your pituitary gland to increase the amount of GH that’s coming out in each of the pulses. For patients with milder GH deficiency, the idea is it will restore that back to normal and it is restoring GH in the normal delivery fashion.”
Ibutamoren boosts height velocity
At 1 year, the 1.6 mg/kg ibutamoren group had an annualized height velocity of 8 cm per year. The increase was deemed comparable to the annualized height velocity of 9.7 cm per year observed with human GH. The height velocity was also comparable to several reference groups of children with moderate GH deficiency who received recombinant human GH. Annualized height velocity at 1 year was 6.8 cm per year for 0.8 mg/kg ibutamoren group and 7.3 cm per year for 3.2 mg/kg ibutamoren group.
IGF-I standard deviation scores at 1 year were 0.14 for the 3.2 mg/kg ibutamoren group, –0.21 for the 1.6 mg/kg dose group and –0.48 for 0.8 mg/kg ibutamoren group compared with 0.74 for those receiving human GH.
Researchers also analyzed height velocity from children receiving 1.6 mg/kg or 3.2 mg/kg ibutamoren from the OraGrowtH210 trial and combined it with children who received ibutamoren in the OraGrowtH212 phase 2 pharmacokinetics trial. The combined group was compared with data from a reference group of 3,075 children receiving human GH who had growth data available in the Pfizer International Growth Database (KIGS) in 2010. Annualized height velocity for the combined ibutamoren group was 8 cm per year at 1 year vs. 8.6 cm per year for the human GH group. At 2 years, annualized height velocity was 7.5 cm per year with ibutamoren compared with 6.9 cm per year for the reference group.
No safety signals observed
There were no treatment-related serious adverse events in OraGrowtH210 or OraGrowtH212. No participants dropped out to adverse events and researchers reported no meaningful safety signals.
Dauber said Lumos Pharma plans to move forward with a phase 3 study using the 1.6 mg/kg dose of ibutamoren.
“From this study, they will also have more 12-month data and year-2 data to see how well [height velocity] is sustained,” Dauber said.
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Dauber A, et al. Oral LUM-201 shows similar annualized height velocity to daily rhGH in moderate pediatric growth hormone deficiency (PGHD) with a 1.6 mg/kg/day dose and a promising investigational safety record. Presented at: Pediatric Endocrine Society Annual Meeting; May 2-5, 2024; Chicago.
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