Affibody has announced the completion of the ABY-039 Phase 1 trial, and the termination of the ABY-039 program due to tolerability observations that would limit the target product profile of subcutaneous high dose once monthly maintentance injections.
Based on these observations Alexion has terminated the co-development agreement with Affibody. The termination will become effective June 18, 2020.
ABY-039 is a bivalent antibody-mimetic that targets the neonatal Fc receptor and that has shown potent lowering of plasma IgG titers and very long half-life in healthy volunteers in Phase 1. Its main competitor, efgartigimod, has recently demonstrated the benefit of IgG lowering in patients with myasthenia gravis in Phase 3.
“Although we are disappointed that the ABY-039 program will not continue, it is reassuring to note that our ABY-035 Phase 2 study has exceeded two years of high dose administration in psoriasis patients with excellent safety and tolerability.”
“We have seen clear evidence that our protein engineering efforts were successful in terms of the efficacy and potency of ABY-039. Although we are disappointed that the ABY-039 program will not continue, it is reassuring to note that our ABY-035 Phase 2 study has exceeded two years of high dose administration in psoriasis patients with excellent safety and tolerability. The Phase 2 study is investigating our bispecific IL-17A inhibitor, ABY-035, that shares the molecular format and has a high sequence similarity to ABY-039,” says Fredrik Frejd, CSO of Affibody.
Positive data from Phase 2 trial
Affibody has also announced positive data from its 52-week trial investigating the novel bispecific IL-17A inhibitor ABY-035 in patients with moderate-to-severe psoriasis (“AFFIRM-35”).
The primary endpoint of the Phase 2 AFFIRM-35 double-blind, placebo controlled, 52-week Phase 2 proof-of-concept trial was PASI 90 response defined as an at least 90% improvement of the baseline Psoriasis Area Severity Index (PASI) score after 12 weeks of treatment. In the group that finished the 80 mg Q2W induction period 15 out of 17 patients (88%) achieved a PASI 90 response and 10 out of 17 patients (59%) achieved complete or almost complete disease remission with an absolute PASI of 1 or below. The overall PASI 90 response at week 12 was 71% for all 21 subjects randomized to the 80 mg Q2W group.
Over one year, 17 out of 21 (81%) subjects in the 80 mg Q2W induction group and 18 out of 22 (82%) subjects in the 160 mg Q2W induction group achieved an absolute PASI of 1 or below and in general maintained a complete or almost complete disease remission with once monthly dosing. The majority of reported adverse events were mild and resolved during treatment. Overall, ABY-035 treatment appeared tolerable and safe.
“Our Phase 2 AFFIRM-35 trial in patients with moderate-to-severe psoriasis has shown excellent and sustained clinical response in patients. Most patients are continuing ABY-035 treatment in an ongoing open label extension study. Based on these promising results, we believe that ABY-035 has best-in-class potential for auto-immune diseases,” said David Bejker, CEO of Affibody. “The patient centric design has also enabled us to comfortably select doses for further development.”
Based on these encouraging clinical results in patients with moderate-to-severe psoriasis, the clinical development program of ABY-035 has been expanded to include further indications for development and commercialization.
“In this patient centric study, we saw direct therapeutic benefit to psoriasis patients by utilizing an experimental medicines adaptive design based on the absolute disease scores of each patient”, said Fredrik Frejd, CSO of Affibody. “Furthermore, the excellent safety and tolerability observed is highly promising, and is important for the Affibody® platform, with repeated high dose administration exceeding two years in a substantial proportion of the patients. The low molecular weight of the molecule enables a very effective way of delivering the drug subcutaneously in a convenient outpatient setting.”
AFFIRM-35 enrolled 108 moderate-to-severe psoriasis patients in centers throughout Germany to evaluate the efficacy, safety and tolerability of ABY-035. In addition to the PASI 90 primary efficacy measure, secondary endpoints included absolute and relative PASI-measures at weeks 12, 24, and 52; DLQI; itch and pain VAS; safety and tolerability, and pharmacokinetics. The core study has now been completed and continues in an open label extension study to gather further data, with some patients having been treated already more than two years with ABY-035. For additional information about the Phase 2 study, please visit www.clinicaltrials.gov (NCT03591887).
ABY-035 doses of 2 mg, 20 mg, 80 mg, 160 mg and placebo were dosed in patients with moderate-to-severe psoriasis. The study comprised an induction period until week 12, followed by a patient centric response guided dose optimization period until week 24, and an individualization period allowing for response guided treatment interval prolongation until week 52.
Photo of Fredrik Frejd: Affibody