Growth Hormone Therapy In Patients Research Articles

Expert Opinion on the Management of Growth Hormone Deficiency in Brain Tumor Survivors: Results From an Italian Survey.

BackgroundGrowth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT).AimsThis study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS.MethodsA multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers).ResultsThe online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD.ConclusionsThe results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD.

Pituitary function and the response to GH therapy in patients with Langerhans cell histiocytosis: analysis of the KIMS database.

ObjectiveTo analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database).Patients and methodsPatients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis.ResultsAt baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and −0.5 (−1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (−1.5 to −0.3 (mmol/L); P < 0.05); AGHDA-QoL-score (n = 20) was improved by 2.8 points (−5.6 to 0.0; P < 0.05), while mean BMI increased 0.6 ± 3 kg/m2 (95% CI: −0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported.ConclusionAfter 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.

Growth Hormone Deficiency and Treatment in Childhood Cancer Survivors.

Growth hormone (GH) deficiency is a common pituitary hormone deficiency in childhood cancer survivors (CCS). The identification, diagnosis, and treatment of those individuals at risk are important in order to minimize associated morbidities that can be ameliorated by treatment with recombinant human GH therapy. However, GH and insulin-like growth factor-I have been implicated in tumorigenesis, so there has been concern over the use of GH therapy in patients with a history of malignancy. Reassuringly, GH therapy has not been shown to increase risk of tumor recurrence. These patients have an increased risk for development of meningiomas, but this may be related to their history of cranial irradiation rather than to GH therapy. In this review, we detail the CCS who are at risk for GHD and the existing evidence on the safety profile of GH therapy in this patient population.

Safety of Growth Hormone Therapy in Patients with Idiopathic Short Stature: A Systematic Review

Safety of Growth Hormone Therapy in Patients with Idiopathic Short Stature: A Systematic Review

Adult Height in 299 Patients with Turner Syndrome with or without Growth Hormone Therapy: Results and Literature Review

Context: Treatment with growth hormone (GH) is considered effective in improving adult height (AH) in Turner syndrome (TS). However, there are few studies comparing AH between treated patients and a concurrent untreated group. Objective: To assess the efficacy of GH treatment in improving AH in TS and to review previous published studies with treated and untreated groups. Participants and Methods: We retrospectively analyzed clinical data and AH of a large cohort of GH-treated (n = 168) and untreated (n = 131) patients with TS. Data are shown as median and interquartile range (IQR). We assessed pretreatment variables related with AH and compared our results with 16 studies that also included an untreated group. Results: The GH-treated group was 6.2 cm taller than the untreated group (AH = 149 cm [IQR 144.5–152.5 cm] vs. 142.8 cm [IQR 139–148 cm], p < 0.001) after 4.9 years of GH treatment with a dose of 0.35 mg/kg/week. AH SDS corrected for target height (TH) was 7.2 cm higher in GH-treated patients. AH SDS ≥−2 was more frequent in GH-treated patients (43%) than in untreated patients (16%, p < 0.001). AH SDS was also more frequently within the TH range in the GH-treated group (52%) than in the untreated group (15%, p < 0.001). Height SDS at start of GH therapy and TH SDS were positively correlated with AH (p < 0.001; R² = 0.375). Considering the current result together with previous similar publications, a mean AH gain of 5.7 cm was observed in GH-treated (n = 696) versus untreated (n = 633) patients. Conclusions: Our study strengthens the evidence for efficacy of GH therapy in patients with TS from different populations.

The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy

BackgroundWolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants.MethodsIn our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature.ResultsA novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years.ConclusionsHere we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome.

Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study.

BackgroundNoonan syndrome is an autosomal dominant condition with an incidence of 1:1000 to 1:2500. The disorder is associated with distinct dysmorphic features, cardiac anomalies, developmental delay and delayed puberty. Short stature is a recognised feature of Noonan syndrome.ObjectivesThe aim of this study is to assess the effect of growth hormone treatment in patients with Noonan syndrome.MethodsRetrospective data was collected from patients with Noonan syndrome treated with growth hormone. The results were analysed with variables expressed as mean values and standard deviation scores.ResultsTwelve Noonan syndrome patients (M: F = 10:2) treated with growth hormone were identified. The mean age of starting growth hormone was 8 years, with baseline height standard deviation score of -2.96 (range: -1.64 to -5.54). The height standard deviation score significantly improved to -2.50 (P = 0.0035) and then -2.22 (P = 0.0025), following one and two years of treatment, respectively. The average height velocity for the patients prior to starting treatment was 5.16cm/year (range: 2.4 - 8.2 cm/year), which significantly improved to 7.76cm/year (ranging from 4.1 to 12.8 cm/year) after one year of growth hormone treatment (P = 0.020) and to 6.51cm/year at the end of two years.ConclusionsOur study has shown that growth hormone treatment significantly improves the height standard deviation score of patients with Noonan syndrome over a two-year course of growth hormone therapy without any side effects. Further research is required to analyse the long-term effect of growth hormone therapy in patients with Noonan syndrome, including the impact on final adult height.

SAT-106 Growth Hormone Treatment Response in Children

OBJECTIVES: Growth hormone (GH) therapy is an effective treatment in addressing growth failure in children with GH deficiency (GHD). It has also been increasingly used in non-GH deficient (nGHD) conditions. We sought to report the growth response of GHD and nGHD patients who received GH therapy at a tertiary care center. METHODS: Data was collected from health records of patients followed in the endocrinology clinic at Alberta Children’s Hospital, Calgary, Canada, from 2005 to 2019, and used to analyze clinical responses based on indication for GH treatment. RESULTS: A total of 167 patient records (87 males and 80 females) were used for analysis. The average age at the start of GH therapy was 7.3 years (range 0.25 to 16.98 yrs). 74 patients were in the GHD group while 93 were nGHD. Of the patients in the nGHD group, the most common diagnosis were: idiopathic short stature (ISS)(n=45), Turner syndrome (TS)(n=26), and Prader Willi Syndrome (PWS)(n=8). The mean height velocity (HV) in year 1 was highest in the GHD group at 11.68 cm/year (n= 62, sd = 5.93), followed by ISS at 9.41cm/year (n = 52, sd = 4.34). The mean first year HV of those who had received chemotherapy (n= 5, mean = 5.48, sd = 1.92) or had Turner syndrome (n= 24, mean = 7.20, sd = 2.15) was significantly lower than both the GHD and ISS groups. GH peak during a GH stimulation test at baseline was not correlated to the first year height velocity while on GH treatment. However there was a negative linear correlation between baseline IGF1 level and first year height velocity (Spearman’s rho = 0.312216, p-value= 0.01516). Age at GH initiation was negatively correlated with height velocity during GH treatment. Height velocity over time decreased sharply from year 1 to year 3, and became stable for the remaining years of GH therapy. For the entire group, HV for years 1-5 was 9.81 (sd=4.83), 7.40 (sd=2.89), 6.29 (sd=2.38), 5.92 (sd=2.56), 5.66 (sd=2.51). There is no significant correlation between GH dose and height velocity response after adjusting for diagnosis. CONCLUSION: In our population, the response to GH therapy was consistent with those reported in the literature. Response to GH therapy was not associated with GH peak on stimulation but rather to baseline IGF-1 level and age at initiation. Although peak GH to stimulation is required to obtain public funding for GH therapy, these findings demonstrate that GH stimulation test results may not indicate which patients may benefit the most from GH therapy. Follow-up until final adult height will allow us to have a better understanding of the efficacy of GH therapy in patients with both GHD and nGHD conditions.

SAT-088 The Incidence of Neurological Symptoms During Growth Hormone Therapy in Patients with Chiari Malformation

Background: Patients (PTs) with Chiari malformation (CM) are prone to a wide variety of neurologic symptoms (SX), including headaches (HA), vision abnormalities, and nausea. These SX are attributed to impaired flow of CSF leading to benign intracranial hypertension (BIH). Occasionally, PTs with CM may require growth hormone therapy (GHT). This can potentially increase CSF accumulation and risk of BIH. The literature is limited to a small number of case reports on GHT in PTs with CM. Here, we describe the incidence of neurologic SX in 15 PTs. Methods: Our database was queried for PTs with CM who were treated with GHT from 2010–18 and records were reviewed for adverse events. PTs with neoplastic disease, active inflammation, or acute trauma were excluded. CM was defined as cerebellar tonsils located below the foramen magnum on MRI. Results: Mean and median ages of the 15 PTs (10 male, 5 female) who met inclusion criteria were 15.3 and 11.7 years, respectively. 14 were diagnosed as Type 1 and 1 was diagnosed as Type 2 CM. Tonsillar displacement ranged from 2-21mm, but was not specified in 5 PTs. Indications for GHT included isolated GH deficiency, panhypopituitarism, and chronic renal disease. Duration of GHT ranged from 0.2 to 12.25 years with a mean and median of 3.7 and 1.75 years, respectively. 7% (1 of 15) PTs experienced new-onset SX of BIH that could be attributed to GHT.8 PTs (53.3%) did not experience any SX consistent with CM before, during, or after GHT. 3 PTs (20%) experienced neurologic SX prior to GHT. 1 PT reported diplopia and abnormal sleep patterns prior to GHT that resolved and did not recur during GHT. 1 PT prior to GHT manifested papilledema, 1 seizure, central sleep apnea, and occipital HA that resolved after posterior fossa decompression. Post-operatively and during GHT, this PT developed and continued to manifest nonpathologic pseudopapilledema. 1 PT continued to have pre-existing seizures and insomnia that did not worsen with GHT. 1 PT (7%) had congenital neurologic abnormalities in addition to CM. This PT had surgery to alleviate BIH caused by congenital hydrocephalus and SX permanently resolved. GHT has been continuous since birth with no new manifestations of CM reported post-operatively. 2 PTs (13%) developed new-onset neurologic SX while on GHT. 1 PT with diabetes experienced HA, 1 report of loss of consciousness, and 1 instance of apnea during periods of hyperglycemia. It was determined that these SX were unrelated to BIH and GHT was not interrupted. 1 PT experienced mild HA and 1 episode of occipital pounding with emesis during GHT. These SX resolved without intervention and GHT was continued without interruption. Despite the complexity of these cases, 0 PTs discontinued GHT. Conclusion: Our study demonstrates that in a majority (93%) of cases, GHT does not cause onset or worsening of SX of BIH in PTs with complicated and uncomplicated CM. GHT should be regarded as a safe treatment in these PTs.

Benefits and challenges in conducting long-term growth hormone therapy in patients with Prader-Willi syndrome

The purpose of this report is to comment the results from long-term growth hormone (GH) treatment of Bulgarian patients suffering from rare genetic disease-Prader-Willi syndrome (PWS) with reference to the age, body composition, complications and genetic etiology. Statistical analysis was performed by ANOVA with post hoc Kruskal-Wallis test and Dunn's multiple comparison tests. In 90% of the patients maternal uniparental disomy (mUPD) was found to be the cause of the disease. No cases due to imprinting defects are found. The BMI data shows no statistically significant difference between BMI at diagnosis (21.850), at the beginning of the GH therapy (21.852) and current BMI (24.09) - measured under the GH background. Early GH treatment allows to overcome arising obstacles in time and to improve the quality of life for PWS children and their families. During the fourteen years study period only ten patients were diagnosed with the disease. Ninety percent (n=9) of the children were found to be with maternal UPD (mUPD) and only one case was due to deletion in 15q11-13. These results are in agreement with other studies in the field which shows the need for reassessment and new robust statistical analysis of the frequency of genetic mechanisms for PWS.

Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature.

Purpose Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children's Hospital. Results Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.

Efficacy and Safety Evaluation of Human Growth Hormone Therapy in Patients with Idiopathic Short Stature in Korea - A Randomised Controlled Trial.

This trial evaluated the efficacy and safety of growth hormone (GH) therapy (Norditropin®; Novo Nordisk, Bagsværd, Denmark) in paediatric patients with idiopathic short stature (ISS) in Korea. This was an open-label, parallel-group, multicentre, interventional trial (ClinicalTrials.gov identifier: NCT01778023). Pre-pubertal patients (mean age 6.2 years; height, 107.1 cm) were randomised 2:1 to 12 months' GH treatment (0.469 mg/kg/week; group A, n=36) or 6 months untreated followed by 6 months' GH treatment (group B, n=18). Safety analysis was based on adverse events (AEs) in all GH-treated patients. After 6 months, height velocity (Ht-V), change in both height standard deviation score (Ht-SDS) and insulin-like growth factor 1 (mean difference [95% confidence interval {CI}]: 5.15 cm/year [4.09, 6.21]; 0.57 [0.43, 0.71]; 164.56 ng/mL [112.04, 217.08], respectively; all p<0.0001) were greater in group A than in group B. Mean difference in Ht-V for 0-6 months versus 6-12 months was 2.80 cm/year (95% CI 1.55, 4.04) for group A and -4.60 cm/year (95% CI -6.12, -3.09; both p<0.0001) for group B. No unexpected AEs were reported. During the first 6 months, height was significantly increased in GH-treated patients versus untreated patients with ISS. Safety of GH was consistent with the known safety profile.

Growth hormone therapy in patients with Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.

Adherence and long-term outcomes of growth hormone therapy in patients from the UK: the easypod connect observational study (ECOS)

Adherence and long-term outcomes of growth hormone therapy in patients from the UK: the easypod connect observational study (ECOS)

Adherence to Growth Hormone Therapy in Patients with Growth Hormone Deficiency Following Traumatic Brain Injury

Adherence to Growth Hormone Therapy in Patients with Growth Hormone Deficiency Following Traumatic Brain Injury

Growth hormone treatment in patients with ataxia telangiectasia

Introduction: Ataxia telangiectasia (A-T) is a devastating autosomal recessive disorder with chromosomal instability and growth failure. Low levels of growth hormone (GH) and growth factors may be related to advanced neurological deterioration, wasting syndrome and more pronounced immunodeficiency.Objective: The objective of this study is to study safety and effectiveness of GH therapy in patients with A-T and evaluate the effect of GH on ataxia and lymphocyte subsets.Methods: Three patients with classical A-T were treated with GH (0.3 mg/kg/d) for 1 year. Growth rate, ataxia score and lymphocyte subsets were monitored.Results: GH treatment was well tolerated. All patients showed a significant increase of height SDS of +1.3 (mean height SDS −1.994), a mean increase of 8 (6–11) cm/12 months. Lymphocytes subsets and ataxia were not altered before and after GH treatment.Conclusions: Treatment with GH is feasible and effective in A-T patients with severe growth arrest, but no effect on ataxia and lymphocytes could be recorded.

Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation in FAM111A gene

BackgroundHypoparathyroidism in children is a heterogeneous group with diverse genetic etiologies. To aid clinicians in the investigation and management of children with hypoparathyroidism, we describe the phenotype of a 6-year-old child with hypoparathyroidism and short stature diagnosed with Kenny-Caffey syndrome (KCS) Type 2 and the subsequent response to growth hormone (GH) treatment.Case presentationThe proband presented in the neonatal period with hypocalcemic seizures secondary to hypoparathyroidism. Her phenotype included small hands and feet, hypoplastic and dystrophic nails, hypoplastic mid-face and macrocrania. Postnatal growth was delayed but neurodevelopment was normal. A skeletal survey at 2 years of age was suggestive of KCS Type 2 and genetic testing revealed a novel de novo heterozygous mutation c.1622C > A (p.Ser541Tyr) in FAM111A. At 3 years and 2 months, her height was 80cms (SDS −3.86). She had normal overnight GH levels. GH therapy was commenced at a dose of 4.9 mg/m2/week for her short stature and low height velocity of 5cms/year. At the end of the first and second years of GH treatment, height velocity was 6.5cms/year and 7.2cms/year, respectively with maximal dose of 7.24 mg/m2/week.ConclusionThis case highlights the phenotype and the limited response to GH in a child with genetically proven KCS type 2. Long-term registries monitoring growth outcomes following GH therapy in patients with rare genetic conditions may help guide clinical decisions regarding the use and doses of GH in these conditions.

Long-term follow-up results of growth hormone therapy for patients with adult growth hormone deficiency

Long-term follow-up results of growth hormone therapy for patients with adult growth hormone deficiency

Long-term follow-up results of growth hormone therapy for patients with adult growth hormone deficiency.

We evaluated the long-term effects of growth hormone (GH) on markers of quality of life, glucose metabolism, and lipid metabolism to validate the adequacy of long-term GH replacement therapy for adult GH deficiency (AGHD). Eighty-three of 100 sequentially followed patients who received GH therapy were selected for this study. Forty-nine were men aged 26 to 78 years (mean, 52 years) and 34 were women aged 20 to 78 years (mean, 56 years). The GH-releasing peptide-2 stimulation test and arginine stimulation test were used to diagnose AGHD. The adult hypopituitarism questionnaire (AHQ) and biochemical parameters such as cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, and gyrated hemoglobin (HbA1c) were determined before treatment, at 6 months of treatment, and at 1, 2, 3, 4, 5, 6, 7, and 8 years of treatment. Considering age and sex as factors potentially influencing the effect of GH therapy, the patients were divided into age groups of <60 and ≥60 years and sex groups of men and women. Repeated measured analysis of variance (ANOVA) was employed. ANOVA demonstrated significant changes in mean AHQ scores during follow-up. Comparison of individual AHQ scores with baseline values revealed sequential improvements, stabilization, and decline in QOL. A significant elevation in HbA1c level was demonstrated. LDL-C and HDL-C levels changed significantly upon GH treatment regardless of sex or age. Levels of glucose, TC or TG did not change significantly. The effect of GH therapy on QOL showed sequential improvements and stabilization until 6-year follow-up.

ENHANCING THE LONGEVITY AND IN VIVO POTENCY OF THERAPEUTIC PROTEINS: THE POWER OF CTP

The relatively short serum half-life of polypeptides poses a challenge in the design of protein therapeutics. Extending the half-life and bioavailability while maintaining safety and efficacy has been attempted using various techniques such as sustained-release preparations and long-acting conjugations. A novel, alternative approach involves the fusion of a natural polypeptide, the C-terminal peptide (CTP) of human chorionic gonadotropin (hCG), to the target protein. The fertility drug FSH-CTP (Elonva®) was the first CTP-containing protein to receive marketing approval. This versatile platform has been utilized to improve the pharmacokinetic (PK) and pharmacodynamic (PD) properties of additional target proteins from different families. This includes CTP fused to erythropoietin (EPO), interferon beta (IFNβ) and coagulation factors VII and IX, as well as thyroid-stimulating hormone (TSH), oxyntomodulin, and growth hormone (GH). Two long-acting, CTP-containing chimeras are currently in clinical development by OPKO Biologics. Long-acting FVIIa-CTP (MOD-5014) is being developed for the treatment of hemophilia with an expected dosing regimen of 2-3 times a week. MOD-5014 exhibited improved in vivo PK/PD, coagulation, and safety parameters in comparison to rFVIIa. This supports the upcoming clinical evaluation of MOD-5014 in hemophilic patients. Long-acting CTP-modified hGH (MOD-4023), currently in advanced clinical development by OPKO, may replace current GH therapy in patients suffering from GH deficiency (GHD) by requiring fewer injections. Animal studies showed that once-weekly administration of MOD-4023 resulted in favorable weight gain response in comparison to daily hGH and established an excellent safety profile. A Phase 1 study in healthy volunteers and Phase 2 trial in GHD patients confirmed the safety and tolerability of MOD-4023 in adults; a pivotal Phase 3 study in GHD adults in ongoing. A recently completed Phase 2 study in GHD children demonstrated an improved PK/PD profile and efficacy for once-weekly MOD-4023 in comparison to daily hGH, supporting OPKO's upcoming Phase 3 trial in pediatric GHD patients. Based on recent pre-clinical and clinical experience, CTP technology was proven a valid, flexible platform for the generation of safe and effective long-acting protein therapeutics, with the potential to offer an improved treatment for patients and better quality of life.