WHAT IS PEDIATRIC GROWTH HORMONE DEFICIENCY (PGHD)?
Growth hormone (GH) deficiency is the consequence of low or absent secretion of growth hormone from the pituitary gland. This results in low GH in the body, inadequate production of downstream signaling molecules required for growth and the subsequent state of growth hormone deficiency (GHD). In children, this rare disorder is termed pediatric growth hormone deficiency (PGHD).
Secretion of GH is under strict hormonal feedback control. Growth hormone-releasing hormone (GHRH) and ghrelin are stimulators of its production while somatostatin produces a strong inhibitory action.
GH is the most important hormone regulating growth in childhood and adolescence which ultimately determines adult height.
CAUSES OF PGHD
PGHD can be congenital (children are born with the condition), acquired (brain tumor, head injuries or other causes), iatrogenic (induced by treatment for cancer), or idiopathic (of unknown cause), and ranges from severe to moderate.
We believe our therapeutic can improve the lives of patients with PGHD
In children, PGHD results in and manifests as slower than normal growth. Children are usually diagnosed by approximately seven years of age due to short stature and stunted growth velocity, although some children are not diagnosed until delay in pubertal growth spurt. About 1 in 4000 children are diagnosed with PGHD.
PGHD is generally diagnosed by clinical observations and multiple tests, including radiographic assessment of bone age and tests of other hormones.
GH release stimulation tests are often needed to confirm PGHD diagnosis.
Current treatment options are limited to daily injectable formulations of recombinant human growth hormone (rhGH). Treatment should be started as soon as PGHD diagnosis is confirmed. Long-term (5 years or longer) treatment is not uncommon to achieve “catch-up” growth and reach full height potential. Unfortunately, daily injections are sometimes not well-accepted by children, and long-term compliance with treatment can be an issue. Lack of compliance has been shown to result in reduced effectiveness of the therapy.
Treatment response is assessed by measurement of height and growth velocity. Treatment is usually continued until final height, completion of skeletal bone maturation (epiphyseal closure), or both have been recorded.
The main therapeutic goal of growth hormone treatment in children with PGHD is to enable these children to achieve normal height, with accompanying improvement of the psychosocial problems related to short stature.
LUM-201, also known as ibutamoren mesylate, is a potent, orally administered small molecule that promotes the secretion of GH from the pituitary gland.
LUM-201 has been demonstrated to increase the release of growth hormone in humans in a pulsatile manner which mimics natural secretion of GH. This increases its downstream effector molecules.
LUM-201 has been studied in more than 1200 people (~200 children and~1000 adult and elderly patients), and was generally well tolerated.
Pediatric Growth Hormone Deficiency has a number of different causes, not all patients will benefit from treatment with LUM-201. Pituitary function tests will enable clinicians to determine which patients may benefit from LUM-201.
- Require a functioning hypothalamic pituitary adrenal (HPA) axis
- Potential to secrete growth hormone
- LUM-201 will stimulate secretion of growth hormone
- Approximately 70% of children with PGHD
- Non-functioning hypothalamic pituitary adrenal (HPA) axis
- Unable to secrete growth hormone
- Does not respond to LUM-201
- Approximately 30% of children with PGHD
Lumos Pharma initially intends to develop LUM-201 as an orally administered product to treat children with growth hormone deficiency. Recombinant human GH is approved for use many other rare indications beyond PGHD including adult GHD, Turner syndrome, SHOX deficiency disorder, and several others. Lumos Pharma plans to develop additional indications for LUM-201.
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GHD INFORMATIONAL SOURCES
Short Stature: Comparison of WHO and National Growth Standards/References for Height – Henrik Thybo Christesen, Birgitte Tønnes Pedersen, Effie Pournara, Isabelle Oliver Petit, Pétur Benedikt Júlíusson – PLOSone
Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth – Wayne S. Cutfield, Jose ́ G. B. Derraik, Alistair J. Gunn, Kyle Reid, Theresa Delany, Elizabeth Robinson, Paul L. Hofman – PLOS One