Recombinant Human PH20: Baseline Analysis of the Reactive Antibody Prevalence in the General Population Using Healthy Subjects.

BACKGROUND: Recombinant human PH20 (rHuPH20) is used to depolymerize hyaluronan in the subcutaneous space, increasing the dispersion and absorption of co-administered drugs. While ~ 5 to 10% of rHuPH20 treatment-naïve healthy volunteers have demonstrated rHuPH20-reactive antibodies, associations with age, sex, fertility, and immune disorders remain unknown.

OBJECTIVES: Using demographically diverse healthy volunteers, we assessed the prevalence of rHuPH20-reactive antibodies in the general population and potential associations with fertility and autoimmunity diseases.

METHODS: In total, 896 subjects aged ≥ 12 years (767 adults; 129 children) without prior exposure to rHuPH20 were enrolled. A demographic and limited medical history review was performed, and K3-EDTA-anticoagulated plasma was analyzed for rHuPH20-reactive antibodies using a bridging immunoassay.

RESULTS: Adult and pediatric positivity rates for rHuPH20-reactive antibodies were 5.2% (40/767) and 1.6% (2/129), respectively. Titers ranged from 5 to 2560 (median 30). In five antibody-positive subjects from whom repeated samples were available, antibody titers remained unchanged or decreased fourfold over periods up to 590 days. The prevalence of rHuPH20-reactive antibodies significantly increased with age (p = 0.0006) and was significantly higher in males than in females (p = 0.0010). Men who had fathered children had a significantly increased prevalence of rHuPH20-reactive antibodies than men who had not (p = 0.0036), whereas the rate of childbearing was not significantly different between rHuPH20 antibody-positive and -negative women. The prevalence between racial/ethnic groups was not significantly different, nor was the presence/absence of an autoimmune disorder.

CONCLUSIONS: Approximately 1/20 of the adult population had rHuPH20-reactive antibodies. The reason remains unknown; however, no evidence for a negative effect on fertility or association with autoimmune disease was demonstrated.