Mecasermin 40mg/4ml solution for injection vials

Mutations in the insulin receptor (INSR) gene underlie rare severe INSR-related insulin resistance syndromes (SIR), including insulin resistance type A, Rabson–Mendenhall syndrome and Donohue syndrome (DS), with DS representing the most severe form of insulin resistance. Treatment of these cases is challenging, with the majority of DS patients dying within the first two years of life. rhIGF-I (mecasermin) has been reported to improve metabolic control and increase lifespan in DS patients. A case report and literature review were completed. We present a case involving a male patient with DS, harbouring a homozygous mutation in the INSR gene (c.591delC). Initial rhIGF-I application via BID (twice daily) injection was unsatisfactory, but continuous subcutaneous rhIGF-I infusion via an insulin pump improved weight development and diabetes control (HbA1c decreased from 10 to 7.6%). However, our patient died at 22 months of age during the course of a respiratory infection in in Libya. Currently available data in the literature comprising more than 30 treated patients worldwide seem to support a trial of rhIGF-I in SIR. rhIGF-I represents a treatment option for challenging SIR cases, but careful consideration of the therapeutic benefits and the burden of the disease is warranted. Continuous application via pump might be advantageous compared to single injections.

Abstract licence: CC BY 4.0

Abstract Objective To measure the efficacy of mecasermin (recombinant human insulin‐like growth factor 1, rh IGF ‐1), for treating symptoms of Rett syndrome ( RTT ) in a pediatric population using a double‐blind crossover study design. Methods Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rh IGF ‐1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28‐week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale ( ADAMS ) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire ( RSBQ ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale ( PTSVAS ) top three concerns, Clinical Global Impression ( CGI ), Parent Global Impression ( PGI ), and the Kerr severity scale. Cardiorespiratory‐ and electroencephalography ( EEG )‐based biomarkers were also analyzed. Results There were no significant differences between randomization groups. The majority of AE s were mild to moderate, although 12 episodes of serious AE s occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography ( EEG ) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation As in the phase 1 trial, rh IGF ‐1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

Abstract licence: CC BY-NC-ND 4.0

Rett Syndrome (RTT) is a severe neurodevelopmental disorder characterized by an apparently normal development followed by an arrest and subsequent regression of cognitive and psychomotor abilities. At present, RTT has no definitive cure and the treatment of RTT represents a largely unmet clinical need. Following partial elucidation of the underlying neurobiology of RTT, a new treatment has been proposed, Mecasermin (recombinant human Insulin-Like Growth Factor 1), which, in addition to impressive evidence from preclinical murine models of RTT, has demonstrated safety in human studies of patients with RTT. The present clinical study examines the disease severity as assessed by clinicians (International Scoring System: ISS), social and cognitive ability assessed by two blinded, independent observers (RSS: Rett Severity Score), and changes in brain activity (EEG) parameters of ten patients with classic RTT and ten untreated patients matched for age and clinical severity. Significant improvement in both the ISS (p = 0.0106) and RSS (p = 0.0274) was found in patients treated with IGF1 in comparison to untreated patients. Analysis of the novel RSS also suggests that patients treated with IGF1 have a greater endurance to social and cognitive testing. The present clinical study adds significant preliminary evidence for the use of IGF-1 in the treatment of RTT and other disorders of the autism spectrum.

Abstract licence: CC BY 4.0

ContextThe Global Increlex® Growth Forum Database (IGFD) Registry monitors real-world effectiveness and safety of recombinant human IGF-1 (rhIGF-1; Increlex® [mecasermin]) treatment in children and adolescents with severe growth failure due to severe primary IGF-I deficiency (SPIGFD).ObjectiveTo report characteristics, effectiveness, and safety data from patients receiving rhIGF-1 treatment who achieved near-adult height (NAH), and determine factors that predict height gain to NAH.MethodsDescriptive analyses of patients included in the Global IGFD Registry (NCT00903110) who achieved NAH are reported for the overall population, treatment-naïve prepubertal (NPP) patients, and patients with Laron syndrome. Linear regression analyses of height gain to NAH are also reported.ResultsOne hundred and two patients enrolled in the Global IGFD Registry achieved NAH at data cut-off (April 20, 2023). Mean age at rhIGF-1 treatment initiation was 11.8 years; median treatment duration was 3.9 years. Mean (SD) height SD score (HtSDS) gain from rhIGF-1 initiation to NAH was 0.9 (1.1). In NPP patients, mean (SD) HtSDS gain was 1.4 (1.0). Almost half of NPP patients reached NAH within the normal range. Despite improved height in patients with Laron syndrome, only 10.5% reached NAH within the normal range; 3 patients with Laron syndrome were NPP. Treatment naivety was predictive of height gain in the overall NAH population. Safety data aligned with previous reports.ConclusionIn a real-world setting, despite patients with SPIGFD initiating rhIGF-1 treatment at a relatively advanced age, rhIGF-1 treatment resulted in improved NAH. The greatest improvements in height outcomes were observed in NPP patients.Trial registrationNCT00903110.

Abstract licence: CC BY