Parenteral administration of therapeutic peptides can be associated with generation of anti-drug antibodies (ADAs). The antibodies can be neutralising or non-neutralising, which is of importance for drug safety and efficacy for indications where the peptide is to be administered repeatedly. A special risk for analogues of human peptides is cross reactivity towards the endogenous peptide.
In the ADA Phase 3 trial, the immunogenicity of dasiglucagon (0.6 mg) was tested. The reference product was GlucaGen® (1 mg). Patients were randomly assigned in a 1:1 ratio to receive 3 SC injections of either dasiglucagon or GlucaGen®, with 1 week between doses. Blood samples for ADA analysis were taken before each of the three doses and 35, 60 and 104 days after the first dose. In total 111 T1DM patients received at least one dose and 102 patients completed all three doses.
The primary endpoint was the overall ADA incidence. No patient had any confirmed treatment-induced or treatment-boosted ADA response at any measuring time after dosing. Nausea and vomiting were the most commonly reported IMP-related AEs, reported with similar frequencies for dasiglucagon and GlucaGen® (nausea: 46% and 43%, vomiting: 21% and 15%, respectively). There were no injection site reactions after dasiglucagon administration, whereas eight injection site reactions in 6 patients were noted in the GlucaGen® group.
In conclusion, dasiglucagon had a low potential for generation of ADAs. The low potential for generation of ADA’s and low potential for injection site reactions are of particular importance for the chronic indications pursued with dasiglucagon.