Figure 3.

Proposition for analyses of the effect of ADAs on treatment after switching ADA positive patients from agalsidase-β to PRX-102

As ADA titers against PRX-102 cannot simply be compared with those against agalsidase-α and -β, it may be considered to also monitor the pharmacokinetic profile in ADA-positive patients after switch. One could measure the total concentration of PRX-102 in plasma (yellow), to assess total drug clearance, as well as enzyme activity in plasma (pink), to assess in vivo enzyme inhibition by ADAs. After switching patients whose ADAs have low in vitro cross reactivity to PRX-102 from agalsidase-β to PRX-102, there are three possible scenarios, described as follows. (A) No response: PK curve is normal or slightly lower than normal. PK slope remains unchanged, suggesting no changes in the ADA response (titer and affinity). (B) Most favorable response: PK curves improve to fully normal, suggesting that constant exposure induced further tolerization (ADAs disappear). (C) Least favorable response: PK curves worsen over time, suggesting new ADAs develop (higher titers) with specific affinity to PRX102.