Rare Community Profiles is a Patient Worthy article series of long-form interviews featuring various stakeholders in the rare disease community, such as patients, their families, advocates, scientists, and more.
Rare Community Profiles: Lumos Pharma CMO Dr. Pisit “Duke” Pitukcheewanont Discusses Phase 2 Results in LUM-201 for Pediatric Growth Hormone Deficiency
Dr. Pisit “Duke” Pitukcheewanont is a man on a mission.
Driven to transform the realm of pediatric endocrinology and contribute to the development of better therapies for children with pediatric growth hormone deficiency, Dr. Duke and his team at Lumos Pharma have been working to develop LUM-201.
Unlike traditional growth hormone deficiency treatments, which consist of recombinant human growth hormone and require invasive and time-consuming injections, LUM-201 is an oral secretagogue – a small molecule that promotes the secretion of growth hormone from the pituitary gland. This has the potential to reduce barriers to care and ensure that children with growth hormone deficiency get the treatment that they need.
In his conversation with Patient Worthy, Dr. Duke discusses the signs of pediatric growth hormone deficiency, why he’s drawn to working in endocrinology, and topline results from two Phase 2 studies that highlight the benefits of LUM-201.
Dr. Duke’s Path to Addressing Pediatric GH Deficiency
Dr. Pisit Pitukcheewanont, MD, FAAP, BCMAS received his MD from Chiang Mai University, where he also completed his pediatric residency; later, he completed an internship, residency, and fellowship in diabetes, endocrinology, and metabolism at Le Bonheur Children’s Medical Center and St Jude Research Hospital at the University of Tennessee, Memphis. Following these experiences, Dr. Duke became a faculty physician at the Children’s Hospital in Los Angeles, Keck School of Medicine of the University of Southern California in 1998—he continues to serve there as an Adjunct Professor of Clinical Pediatrics, now poised with over 25 years of combined clinical expertise and research contributions. When asked why he chose to focus on endocrinology, Dr. Duke explained:
“I wanted to go into endocrinology because it’s a very unique field. The endocrine system—you can’t really see it. Sometimes endocrine issues are in the blood, the tissue, the nerves. The mechanisms of endocrine diseases are complex and there’s a lot of interpretation. Pediatric endocrinology fascinated me. My specific expertise is in bone and growth disorders.”
In 2007, Dr. Duke joined the Board of Directors for the Human Growth Foundation, the world’s leading nonprofit organization that is committed to advancing research, educating communities, and providing support for those affected by rare growth, bone, and endocrine conditions. The Human Growth Foundation was established in 1965. At the time, there were no drugs available for pediatric growth hormone deficiency. Says Dr. Duke:
“Growth hormone was sourced from the pituitary gland of cadavers. One of the Human Growth Foundation’s founders realized that this could cause unknown complications for patients, such as degenerative diseases like Creutzfeldt-Jakob disease. So the Human Growth Foundation became committed to funding research to discover and develop therapies that could safely and effectively help those with growth disorders. Since joining the Board of Directors, then becoming President in 2011, I’ve launched our nonprofit for a global scale with significant patients and caregivers to educate general practitioners and specialists. My goal is to provide support for research and education worldwide.”
Prior to joining Lumos Pharma, Dr. Duke served as Vice President, Global Medical Affairs and Vice President, Global Medical Ambassador and Medical Education at Ascendis Pharma. Here, he contributed in spearheading the development and pre-launch strategies for a weekly injectable growth hormone called Skytrofa. Recognizing the burden of daily or weekly injections on families affected by pediatric growth hormone deficiency, Dr. Duke excitedly chose to join Lumos Pharma in May 2022 as Vice President of Global Clinical Development and Medical Affairs. He shares:
“At Ascendis, we worked on a weekly long-acting growth hormone injection that proved effective in treating children with growth hormone deficiency. I wanted to challenge myself by working on another mechanism of action. I chose Lumos Pharma, which is focused on endocrine conditions, where I could work on an oral formulation of a therapeutic that stimulates growth hormone release to reduce the barriers to care for patients and families.”
He later became SVP within the same role before transitioning to Lumos’ Chief Medical Officer in January 2024.
Developing LUM-201 for Moderate Pediatric Growth Hormone Deficiency
Lumos Pharma is developing LUM-201 (ibutamoren) for the treatment of moderate pediatric growth hormone deficiency. PGHD is a rare disorder in which the body doesn’t make enough growth hormone, which leads to an abnormally short height. A child with PGHD is usually normally sized at birth but can develop symptoms later. Says Dr. Duke:
“PGHD has multiple etiologies. Children with this condition may develop hypoglycemia or show signs like convulsions, fine hair and poor nail growth, a high-pitched voice, slow tooth eruption, or what I call ‘doll faces.’ These kids are very cute. If the child looks younger than their age and is very short, that child may have hormone problems. I’ve noticed that parents normally notice height more strikingly in boys, but I want to promote awareness that short stature in females can also suggest PGHD. To parents: if your child is not growing taller compared to their friends, ask your physician. To physicians and school nurses: learn the signs so that you can potentially identify whether someone is just short or whether there is a need to be concerned.”
Pediatric growth hormone deficiency is usually treated with injectable recombinant growth hormone. LUM-201 works by mimicking the body’s natural GH secretion. Lumos Pharma describes LUM-201 as:
“An investigational, once-daily, orally administered small molecule that promotes the secretion of Growth Hormone (GH) from the pituitary gland. LUM-201 has been observed to increase the amplitude of endogenous pulsatile GH secretion, which mimics the natural pattern of GH secretion via potent agonism of the growth hormone secretagogue receptor.”
When asked why LUM-201 stood out to Dr. Duke, he noted that this drug—and its mechanism—are very unique. Ibutamoren was first discovered by Roy Smith and inherited by Dr. Michael Thorner before being explored in the clinical setting. While Skytrofa, another PGHD treatment, was approved for use in 2021, Dr. Duke explains that LUM-201 offers additional benefits to patients, saying:
“Treating GH deficiency could take years. It can be cumbersome. Some patients don’t want currently available treatments because of the injections. There are many obstacles and barriers to care with injections. Some people are needle phobic. Parents work and aren’t always able to supervise. Some injections need to be refrigerated. Patients want options. No oral alternative has ever worked in the past. I view LUM-201 as overcoming this obstacle. Of course, there are still challenges: we need funding to get to the finish line and patients to complete the trials. But I feel confident that we will get there, and I believe that this medication will be impactful and, at the very least, an alternative option for patients who want to receive growth-promoting therapies.”
LUM-201: Phase 2 Study Results
Topline data from two Phase 2 clinical studies evaluating LUM-201 for moderate PGHD highlighted the benefits of the therapy. Altogether, both trials met all primary and secondary endpoints.
The Phase 2 OraGrowtH210 study compared LUM-201 and a daily growth hormone injection. During the course of the trial, researchers also focused on identifying the ideal LUM-201 dose for future studies. 81 participants enrolled across five different countries.
Patients received either 0.8mg/kg, 1.6mg/kg, or 3.2mg/kg LUM-201daily over a 12-month period. The trial found that the 1.6mg/kg daily dose contributed to the highest growth velocity. Says Dr. Duke:
“Patients receiving 1.6mg/kg LUM-201 showed an annual height velocity of 8.2cm/year at six months and 8.0cm/year at 12 months. Real-world data shows that growth velocity on daily injections is in the range of 8.3-8.6cm/year, so LUM-201 produced comparable results. The safety profile to this point is also very promising. While there were a few adverse events related to treatment, there were no serious adverse events and no subjects released from the trial due to adverse events. Ultimately, I found these results to be pretty exciting.”
The second and more mechanistic trial, OraGrowtH212, was a single-site study in Santiago, Chile, that enrolled 22 participants. Researchers checked growth hormone concentration every 10 minute over a 12-hour period between 8am and 8pm at baseline and after six months on LUM-201. Through this, the research team could calculate 24-hour growth hormone levels and analyze secretion. Dr. Duke shares:
“After six months on LUM-201, growth hormone levels normalized. We found that LUM-201 generates a concentration that is only one fifth of the concentration from injections but contributes to comparable GH secretion. Essentially, LUM-201 restored pulsatile GH secretion approximating physiological levels of GH.”
Throughout his experience, Dr. Duke has seen children grow on growth hormone injections. Yet he notes that these injections require doses higher than the normal pituitary secretion. So, he explains, LUM-201 confers benefits because it can stabilize GH levels without requiring higher and higher doses each year, allowing for similar growth.
Moving forward, Lumos Pharma plans to meet with the FDA to analyze existing data and prepare for a Phase 3 study.