The release of encouraging interim results from two Phase II trials of LUM-201 has enabled Lumos Pharma to edge closer towards its goal of bringing the first orally administered therapy for pediatric growth hormone deficiency (PGHD) to market. With a favorable administration route, LUM-201 has the potential to improve low rates of treatment compliance, a significant unmet need in PGHD, according to GlobalData, a leading data and analytics company.

Fiona Chisholm, Managing Analyst at GlobalData, comments: “For decades, the only treatment option available to patients with PGHD has been through injections with recombinant human growth hormone (rhGH). The prospect of an approved oral therapy is an exciting development for patients and their caregivers.”

PGHD is a rare disorder with approximately 14,000 children (aged 0­-11 years) diagnosed in the US, according to GlobalData’s epidemiology database. It is characterized by inadequate secretion of growth hormone from the anterior pituitary gland, which results in stunted growth and requires patients to undergo treatment frequently with daily or weekly injections over many years. According to key opinion leaders (KOLs) interviewed by GlobalData, this can often lead to poor treatment compliance, and, consequently, suboptimal therapeutic outcomes.

Chisholm continues: “The burden of injections can be particularly problematic for pediatric populations. Children are often more susceptible to needle phobia than adults, and this can lead to treatment avoidance or resistance. Recently, treatment options for PGHD have improved due to the emergence of the first long-acting rhGHs, which require weekly rather than daily dosing. However, there is still an unmet need for a safe and effective oral therapy.”

LUM-201 increases the amplitude of endogenous pulsatile growth hormone secretion via potent agonism of the growth hormone secretagogue receptor (GHSR), and, therefore, represents a novel approach to the treatment of PGHD. According to GlobalData’s pipeline product database, it is the only one of eight assets in the late-stage* pipeline that is not a rhGH. If successful, the therapy is likely to be approved for patients with moderate disease**, who account for approximately 60% of the overall PGHD population. In the Phase II trials, the safety and tolerability of LUM-201 was found to be comparable to rhGH and the growth response observed was in line with expectations based on comparisons with historical data from rhGH trials***.

Chisholm adds: “This is an exciting development within the PGHD space. For the first time it appears credible that an oral investigational therapy could demonstrate similar safety and efficacy to rhGH in a PGHD subset. If further data validates this, it will provide Lumos with a unique and compelling marketing strategy for LUM-201.”

*Products in Phase II development or above.

**Patients with moderate PGHD have a functional but reduced hypothalamic pituitary growth hormone (HP-GH) axis, and are therefore capable of secreting some, although insufficient, growth hormone. Conversely, patients with severe PGHD have a non-functional HP-GH axis and are unable to secrete any growth hormone. A Predictive Enrichment Markers (PEMs) strategy uses clinical markers to determine hypothalamic/pituitary function assessment. Moderate (PEM positive) PGHD patients are considered to be likely to respond to LUM-201 while severe (PEM negative) PGHD patients are not expected to respond to LUM-201.

***The interim analysis shows that the growth response of LUM-201 was found to be inferior to rhGH. However, Lumos has attributed this to growth outliers in the rhGH cohort and imbalances in baseline characteristics, as the high growth response in this cohort was inconsistent with data obtained from multiple rhGH historical trials in similarly characterized populations. The company expects this to resolve as the enrollment process progresses, resulting in greater balance across all cohorts.