In this example, we continue to work with the model and analysis from Immuno-modulation in Chronic Inflammation: Clinical Candidate Selection. We are targeting a membrane bound protein, which is often found to be involved in the pathogenesis of Immune thrombocytopenic purpura and Rheumatoid Arthritis, using a monoclonal antibody. The competitor molecule is still ahead in the clinic, dose administration and frequency are still the major Go/No-go criteria, and thus far we have observed high non-linear PK (IV and SC dosing) and high PK variability with SC dosing.
In this case study, we look at whether the non-linear PK and SC PK variability can be explained. Will it be possible to achieve >90% target inhibition in patients and should this program be discontinued?
- The model was updated with clinical data. The model predicted non-linear PK and target occupancy as well as variability in SC dosing.
- The model results were used to amend Ph1 protocol, to prepare Medicine and Marketing for counterintuitive Ph1 results and to obtain regulatory approval to change Ph2 trial design.
- Customer’s best-in-class molecule is now positioned to be first-in-class as well (competitor postponed clinical trials).