Slide 1: Disclosure Slide
Disclosure Slide Financial Disclosure for: Professor Hope Northrup M.D. Director, Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX Investigator in clinical trials sponsored by BioMarin Pharmaceutica
Slide 2: Phase 3 PRISM studies: Efficacy & safety of pegvaliase 60mg in adult patients with PKU
Phase 3 PRISM studies: Efficacy & safety of pegvaliase 60mg in adult patients with PKU Northrup H1, Burton BK2, Zori RT3, Posner J4, Olbertz J5, Lounsbury D5, Weng HH5, Vockley J6 1 University of Texas Health Science Center at Houston, Houston, TX, USA; 2 Lurie Children’s Hospital and the Northweste
Slide 3: Methods
Methods • PRISM-2 Part 4 (see Figure 1) was comprised of an open-label extension, in which subjects could titrate up to 60 mg/day if they had a combined total of >52 weeks of pegvaliase and a minimum of 8 weeks at the 40 mg/day dosage in PRISM-2 and previous studies to achieve a blood Phe level <600
Slide 4: Results: Subject disposition
Results Subject disposition • The mean (SD) pegvaliase dose in the 202 subjects enrolled into Part 4 of PRISM-2 was 33 (13) mg/day, with total pegvaliase exposure of 572 person-years of which there were 96 person-years exposure on 60 mg/day • 51 (25%) subjects comprised the Stable 60 mg dose populat
Slide 5: Results: Efficacy
Results Efficacy • Mean blood Phe for all subjects in Part 4 was reduced from treatment-naïve baseline levels (1226 μmol/L; n=215) to 392 (487) μmol/L (n=182) after 49 weeks of pegvaliase treatment at doses up to 60 mg/day • For the Stable 60 mg/day dose population, mean (SD) blood Phe was 1063 (372
Slide 6: Results: Efficacy
Results Efficacy • Following dose increase to 60 mg, an increase in the proportion of subjects reaching blood Phe thresholds was observed over time (Figure 3): • 38%, 44%, and 64% of subjects reached blood Phe levels ≤600 μmol/L by 12, 24, and 48 weeks on 60 mg/day dose, respectively • 28%, 39%, and
Slide 7: Results: Safety
Results Safety • Of the 202 subjects enrolled in PRISM-2 Part 4, 201 (99.5%) reported at least 1 AE • Overall, the highest severity AE was CTCAE Grade 1 for 5% of subjects, CTCAE Grade 2 for 79%, CTCAE Grade 3 for 15%, and CTCAE Grade 4 for 1.5% of subjects • Seven (3.5%) subjects experienced 11 epi
Slide 8: Results
Results • As AEs are more common in the first 6 months of treatment, when patients are on lower doses, AEs occurring at or after 1 year of treatment were assessed by dose level • During this period, subjects who received at least one 60 mg dose of pegvaliase (n=98, 94.7 person-years of exposure) had
Slide 9: Results: Safety
Results Safety • No subjects experienced episodes of acute systemic hypersensitivity reactions after receiving 60 mg pegvaliase dose in Part 4 , which had a maximum 274 weeks of follow-up • Antibody titers in the Stable 60 mg dose population followed a similar pattern as observed in subjects at all
Slide 10: Conclusions
Conclusions • 25% of subjects in Part 4 of PRISM-2 received stable doses of 60 mg/day • Substantial blood Phe reduction was observed after dose increase to 60 mg/day, which was sustained over time • Safety profile of 60 mg/day dose was consistent with the lower maintenance doses DRAFT MATERIALS
Slide 11: References and Acknowledgements
References 1. van Wegberg AMJ et al. Orphanet J Rare Dis. 2017;12:162. 2. Vockley J et al. Genet Med. 2014;16(2):188–200. 3. Bell SM et al. PLoS One. 2017;12:e0173269. 4. Longo N et al. Lancet. 2014;384:37–44. 5. Sarkissian CN et al. Proc Natl Acad Sci USA. 1999;96:2339–44. 6. Palynziq [package inse