Lumos Reports Positive Topline Data from Phase 2 Studies of Oral Growth Hormone

Rare Daily Staff

Lumos Pharma said that topline results from its phase 2 OraGrowtH210 dose-finding trial and its phase 2 OraGrowtH212 pharmacokinetic/pharmacodynamic trial met all primary and secondary endpoints.

Data from the OraGrowtH210 trial demonstrated annualized height velocity on the 1.6 mg/kg dose of orally administered LUM-201 of 8.2 cm/yr at six months and 8.0 cm/yr at 12 months on treatment, in line with historical data in moderate pediatric growth hormone deficiency (PGHD) patients and within the targeted 2 cm/yr margin of the comparator injectable recombinant growth hormone arm.

Data also provided preliminary validation of the predictive enrichment marker (PEM) strategy, with prespecified primary and secondary outcomes met, which the company said de-risks its patient selection for its phase 3 program.

Pediatric growth hormone deficiency can be congenital, result from disease or injury, induced by treatment for cancer, or have an unknown cause. Consequences of the condition can range from severe to moderate.

LUM-201, also known as ibutamoren, is an experimental, once-daily, orally administered small molecule that promotes the secretion of growth hormone from the pituitary gland. LUM-201 has been observed to increase the amplitude of endogenous pulsatile growth hormone secretion, which mimics the natural pattern of growth hormone secretion via potent agonism of the growth hormone secretagogue receptor.

The OraGrowtH210 trial is a global, multi-site study that assesses the effects of orally administered LUM-201 at three different dose levels in comparison to daily injections of recombinant human growth hormone (rhGH). The trial involves 82 participants diagnosed with moderate pediatric growth hormone deficiency. To enrich the trial population with individuals likely to respond to LUM-201, specific PEM criteria were applied during the screening process. The primary purpose of this study was not to establish efficacy or demonstrate non-inferiority compared to daily growth hormone treatment.

The OraGrowtH212 trial is a single-site, open-label study designed to assess the pharmacokinetic and pharmacodynamic impacts of oral LUM-201. This trial includes up to 24 individuals with no prior treatment for pediatric growth hormone deficiency, who are administered LUM-201 at two different dosage levels. Every participant in the OraGrowtH212 Trial met the criteria for patient PEM positivity, ensuring their potential responsiveness to LUM-201.

Data from the OraGrowtH212 trial confirmed that LUM-201’s pulsatile mechanism produces an increase in growth rates while restoring growth hormone secretion and IGF-1 to within normal range, with levels substantially below those produced by exogenous injectable rhGH.

Additionally, data from a small subset of 10 subjects combined at the moderate and high dosage of LUM-201 in both OraGrowtH210 and OraGrowtH212 trials demonstrated the sustained effectiveness of annualized height velocity up to 24 months. The company said the safety profile for LUM-201 remained clean throughout both phase 2 studies, with no safety concerns identified in either of the phase 2 trials conducted thus far.

The OraGrowtH210 trial met its primary objective, with six-month annualized height velocity data of 8.2 cm/yr supporting at the moderate dose as the optimal dose for a phase 3 clinical trial. The six-month and 12-month annualized height velocity at that dose met expectations for growth and were within the targeted 2.0 cm/yr margin for non-inferiority against injectable rhGH cohort.

Lumos said there was a higher than anticipated annualized height velocity seen in the moderate PGHD population treated in the rhGH control arm of the OraGrowtH210 trial that was inconsistent with multiple historical trials which predicted growth in the 8.3-8.6 cm/yr range for moderate PGHD. The company said the distinctive growth pattern observed in the daily growth hormone arm of this study is likely due to a higher dosage and the presence of outliers. It anticipates that in a larger, more statistically robust phase 3 trial, the annualized height velocity associated with rhGH treatment will align more closely with historical values for the moderate patient population.

The topline results from the OraGrowtH212 Trial reveal that LUM-201 achieved an expected annualized height velocity with only 20 percent of the growth hormone concentration observed using injectable rhGH. This outcome was achieved through LUM-201’s natural pulsatile mechanism, promoting growth in moderate PGHD subjects that align with historical norms. Notably, LUM-201 raised circulating GH to levels closer to normal physiological ranges, whereas treatment with injectable rhGH has been shown to elevate GH levels to four to five times that of typical healthy children. During the first 12 months of LUM-201 treatment, no IGF-1 values exceeded 2 standard deviations from the mean.

The topline results from both the OraGrowtH210 and OraGrowtH212 trials have shown a clean safety record, characterized by an absence of treatment-related serious adverse events. There were no instances of participants discontinuing treatment due to adverse events.

“These findings not only align with historical growth expectations on therapy but also underscore the distinct advantage of LUM-201’s unique pulsatile mechanism,” said Ron Rosenfeld, chairman of Lumos’ clinical and scientific advisory board. “Demonstrating the ability to achieve expected growth with oral LUM-201 while exposing patients to only 20 percent of the growth hormone compared to daily rhGH injections is a significant scientific breakthrough that has the potential to revolutionize the approach to treating children with moderate growth hormone deficiency.”