Evaluating of the Efficacy of Pegvisomant in Treatment of Acromegaly: Analysis of Integrated Clinical Trial Database (ICTD)
Presentation Number: SAT 403
Date of Presentation: April 1st, 2017
Juliana Hendrika Hey-Hadavi*1, Nina Cecilia Camacho-Hubner2, Natasa Rajicic3, Kaijie Pan1 and Jose Francisco Cara1
1Pfizer Inc, New York, NY, 2Pfizer, Dobbs Ferry, NY, 3Pfizer, Inc., New York, NY
Introduction:Pegvisomant (PEGV) is a competitive antagonist of Growth Hormone (GH) and its effects are the result of its reversible binding to the GH receptor. ICTD contains efficacy data from previous PEGV clinical trials. The efficacy of PEGV in subjects with acromegaly was evaluated using this integrated data.
Subjects and Methods: The pegvisomant integrated clinical trial database includes data from 550 unique (non-duplicate) subjects (56% males) who received at least one dose of PEGV and 47 unique placebo subjects (51% males), all of whom were included in the safety analysis. Because subjects may have participated in one or more studies and received more than one dosage of PEGV, a total of 827 subjects (456 (55%) males, mean age 47 yrs., range 20 – 84) enrolled in 13 phase 2b, 3 and 4 clinical trials were included in the efficacy analysis. Studies were of variable length and only the studies with daily dosing were included. IGF-I normalization rates were defined as the percent of subjects who achieved an IGF-I value < 1.2 X ULN at least once at any time during the study, at the end of study, or based on last observation carried forward.
Results:Treatment duration ranged from 6 to 84.7 weeks and average PEGV dose was 7.8 mg to 22.6 mg/day. IGF-I normalization rates ranged from 19.4 to 94.7%, with the highest rate using daily therapy, longer study drug exposure and appropriate dose titration. Over 50% of acromegaly subjects had normalization of IGF-I within 2 weeks. IGF-I normalization was achieved in >50% of subjects in 9 studies, >75% of subjects in 7 studies, and >90% of subjects in 2 studies. Normalization of IGF-I was found to persist throughout 84.7 weeks of treatment. Average duration of the treatment, average dose, and proper PEGV titration appear to be related to the proportion of subjects with IGF-I normalization; adequate titration of PEGV was key for efficacy, as ~95% of subjects had IGF-I normalization with proper PEGV dose titration. Among PEGV patients, 83.8% reported Treatment Emergent Adverse Events (TEAE), and 8.4% discontinued due to AEs. Among PEGV female patient, 89.3% reported TEAE, and 11.6% discontinued due to AEs. Among PEGV male patient, 79.3% reported TEAE, and 5.8% discontinued due to AE. Common adverse events reported by > 10% of PEGV subjects included headache, nasopharyngitis, arthralgia, diarrhea, fatigue and back pain.
Conclusions: PEGV is found to be highly effective in normalizing IGF-I levels in subjects with acromegaly. The integrated data shows that full efficacy of PEGV is contingent upon adequate duration of exposure and suitable dose titration, which ultimately results in IGF-I control in the majority of subjects without evidence of drug tolerance. Review of safety data supports the positive benefit-risk profile.
Disclosure: JHH: Employee, Pfizer, Inc.. NCC: Employee, Pfizer, Inc.. NR: Employee, Pfizer, Inc.. KP: Employee, Pfizer, Inc.. JFC: Employee, Pfizer, Inc..