Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia
Authors' conclusion
Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP
Study context
- Population
- Adults with hypophosphatasia (HPP)5/cohort
- Participants
- 15 adults
- Comparison
- Efzimfotase alfa 15 mg vs 45 mg vs 90 mg
- Cohort 1n = 5
- Cohort 2n = 5
- Cohort 3n = 5
- Outcome
- Safety and tolerability
Methodological detailsfirst-in-human, open-label, dose-escalating
- First-in-human
- Open-label
- Dose-escalating
Main finding
As reported in the abstract
Treatment-emergent adverse events (TEAEs)
12 (80%) participants
Injection site reactions (ISRs)
8 (53%) participants
ISRs after s.c. injections
10 of 41
24%
Secondary outcomes
Pharmacokinetics
- Arithmetic mean elimination half-life
- ≈6 d
- Absolute bioavailability over s.c. 15-90 mg
- 28.6%-36.8%
- Peak and total exposures increased greater-than-dose proportionally over 15-90 mg after i.v. and s.c. dosing
Pharmacodynamics: plasma PPi and PLP
- Dose-dependent reductions vs baseline, nadir in first week after i.v. dosing, sustained 3-4 wk after last s.c. dose
Immunogenicity
- ADA positive
- 4 (27%) participants
- ADA positive before first dose
- 3
- Neutralizing antibodies
- 0
- Antidrug antibodies (ADAs) had no apparent effect on PK/PD
Safety
- TEAEs
- 12 (80%) participants
- ISRs
- 8 (53%) participants
- ISRs after s.c. injections
- 10 of 41 (24%)
- Most ISR TEAEs mild, resolved within 1-2 d
Original publication
Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia. J Bone Miner Res. Published 13 August 2024. doi:10.
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