IMPE2023 Free Communications Growth and Syndromes (4 abstracts)
Predicted Ratio of IGF-1 Observations and Differences in IGF-1 SDS Observations to 96-hour Values Over the Dosing Interval in Pediatric pGHD Patients Receiving Somatrogon
Satyaprakash Nayak 1 , Patanjali Ravva 2 & Joan Korth-Bradley 3
1Pfizer Inc, Cambridge, USA. 2Pfizer Inc, Princeton Junction, USA. 3Pfizer Inc, Collegeville, USA
Background: Somatrogon is a once-weekly treatment for children with pediatric GH deficiency (pGHD). The goal of this study was to simulate IGF-1 and IGF-1 SDS profiles and calculate the ratio and differences of observations to 96-hour values over the dosing interval.
Methods: A population PK model was developed using data from a Phase 2 study and a Phase 3 study in children with pGHD. An indirect-response PK/PD model linked drug concentration with IGF-1. The PK model includes the effect of ADA on somatrogon clearance after 6 months. For each of the ~9000 dosing records, an IGF-1 profile over 168 hours at steady-state was simulated. The ratio of IGF-1 and difference in IGF-1 SDS to values at 96 hours after the previous dose was calculated.
Results: Early in therapy, the mean of the difference of IGF-1 SDS and mean IGF-1 SDS ranged between -0.98 (at 0 and 7 days after dosing) and 0.74 (at day 2 after dosing). After 6 months of treatment, when it is assumed that anti-drug antibodies have resulted in higher somatrogon concentrations, the mean of the difference of IGF-1 SDS and mean IGF-1 SDS ranged between -1.55 (at 0 and 7 days after dosing) and 0.37 (at day 2.5 after dosing). Similar results were observed in simulations assuming doses of 0.66 mg/kg/wk.
| Predicted Difference Between IGF-1 SDS and Average IGF-1 SDS by Time with 90% Prediction Intervals | |||||||
| Less than 6 months of somatrogon | More than 6 months of somatrogon | ||||||
| Day | Mean | 90% PI L | 90% PI U | Day | Mean | 90% PI L | 90% PI U |
| 0 | -0.98 | -2.07 | -0.26 | 0 | -1.55 | -3.36 | -0.06 |
| 0.5 | -0.17 | -1.19 | 0.59 | 0.5 | -0.75 | -2.01 | 0.38 |
| 1 | 0.34 | -0.68 | 1.33 | 1 | -0.22 | -1.24 | 1.18 |
| 1.5 | 0.63 | -0.37 | 1.65 | 1.5 | 0.12 | -0.77 | 1.6 |
| 2 | 0.74 | -0.2 | 1.67 | 2 | 0.3 | -0.46 | 1.73 |
| 2.5 | 0.69 | -0.09 | 1.44 | 2.5 | 0.37 | -0.26 | 1.55 |
| 3 | 0.51 | -0.02 | 1.03 | 3 | 0.33 | -0.12 | 1.16 |
| 3.5 | 0.26 | 0.01 | 0.51 | 3.5 | 0.2 | -0.04 | 0.63 |
| 4 | 0 | 0 | 0 | 4 | 0 | 0 | 0 |
| 4.5 | -0.24 | -0.48 | -0.04 | 4.5 | -0.25 | -0.66 | 0.01 |
| 5 | -0.45 | -0.89 | -0.11 | 5 | -0.52 | -1.3 | 0.01 |
| 5.5 | -0.63 | -1.29 | -0.16 | 5.5 | -0.8 | -1.9 | 0 |
| 6 | -0.78 | -1.6 | -0.21 | 6 | -1.07 | -2.45 | -0.01 |
| 6.5 | -0.89 | -1.85 | -0.24 | 6.5 | -1.33 | -2.94 | -0.03 |
| 7 | -0.98 | -2.07 | -0.26 | 7 | -1.55 | -3.36 | -0.06 |
Conclusions: Simulations such as these may aid clinicians in interpreting IGF-1 levels in pediatric patients with GHD receiving somatrogon.
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