Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study
Fremanezumab, a fully humanized IgG2Δa/kappa monoclonal antibody, selectively targets the calcitonin-gene-related peptide (CGRP) and prevents it from binding to the CGRP receptor. The safety, tolerability, pharmacokinetics (PK), and efficacy of fremanezumab for treating migraines administered as a o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/785 |
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| author | Aksana Jones Orit Cohen-Barak Andrijana Radivojevic Jill Fiedler-Kelly |
| author_facet | Aksana Jones Orit Cohen-Barak Andrijana Radivojevic Jill Fiedler-Kelly |
| author_sort | Aksana Jones |
| collection | DOAJ |
| description | Fremanezumab, a fully humanized IgG2Δa/kappa monoclonal antibody, selectively targets the calcitonin-gene-related peptide (CGRP) and prevents it from binding to the CGRP receptor. The safety, tolerability, pharmacokinetics (PK), and efficacy of fremanezumab for treating migraines administered as a once monthly 225 mg dose or a once quarterly 675 mg dose have been well characterized in adults. The fremanezumab exposure and body weight relationship supported the use of the approved 225 mg monthly adult dose for pediatric patients weighing ≥45 kg. In the pediatric Phase 3 program, a 120 mg dose for patients weighing <45 kg was determined using the results of an open-label study and a population PK modeling and simulation strategy. A thorough evaluation was conducted to further characterize the population PK of fremanezumab and assess the predictive performance of the adult population PK model when applied to the Phase 1 pediatric data, the predictive performance of alternative pediatric population PK models, and the predictive performance of the selected pediatric population PK model via a noncompartmental-based approach. This latter comparison to noncompartmental results provided additional evidence that the pediatric population PK model predicts the observed data well and supports the 120 mg monthly dose in patients weighing <45 kg. |
| first_indexed | 2024-03-10T11:05:45Z |
| format | Article |
| id | doaj.art-c1a782b80316404998e3feabfe0ff830 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:05:45Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c1a782b80316404998e3feabfe0ff8302023-11-21T21:10:59ZengMDPI AGPharmaceutics1999-49232021-05-0113678510.3390/pharmaceutics13060785Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 StudyAksana Jones0Orit Cohen-Barak1Andrijana Radivojevic2Jill Fiedler-Kelly3Cognigen Corporation, Buffalo, NY 14221, USATeva Pharmaceutical Industries, Netanya 4250483, IsraelIntiGrowth LLC, New York, NY 10025, USACognigen Corporation, Buffalo, NY 14221, USAFremanezumab, a fully humanized IgG2Δa/kappa monoclonal antibody, selectively targets the calcitonin-gene-related peptide (CGRP) and prevents it from binding to the CGRP receptor. The safety, tolerability, pharmacokinetics (PK), and efficacy of fremanezumab for treating migraines administered as a once monthly 225 mg dose or a once quarterly 675 mg dose have been well characterized in adults. The fremanezumab exposure and body weight relationship supported the use of the approved 225 mg monthly adult dose for pediatric patients weighing ≥45 kg. In the pediatric Phase 3 program, a 120 mg dose for patients weighing <45 kg was determined using the results of an open-label study and a population PK modeling and simulation strategy. A thorough evaluation was conducted to further characterize the population PK of fremanezumab and assess the predictive performance of the adult population PK model when applied to the Phase 1 pediatric data, the predictive performance of alternative pediatric population PK models, and the predictive performance of the selected pediatric population PK model via a noncompartmental-based approach. This latter comparison to noncompartmental results provided additional evidence that the pediatric population PK model predicts the observed data well and supports the 120 mg monthly dose in patients weighing <45 kg.https://www.mdpi.com/1999-4923/13/6/785pediatric dose selectionfremanezumabpharmacometricspediatric migraine |
| spellingShingle | Aksana Jones Orit Cohen-Barak Andrijana Radivojevic Jill Fiedler-Kelly Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study Pharmaceutics pediatric dose selection fremanezumab pharmacometrics pediatric migraine |
| title | Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study |
| title_full | Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study |
| title_fullStr | Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study |
| title_full_unstemmed | Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study |
| title_short | Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY<sup>®</sup>) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study |
| title_sort | scaling approaches for pediatric dose selection the fremanezumab ajovy sup r sup journey to select a phase 3 dose using pharmacokinetic data from a phase 1 study |
| topic | pediatric dose selection fremanezumab pharmacometrics pediatric migraine |
| url | https://www.mdpi.com/1999-4923/13/6/785 |
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