SynAct Pharma AB (“SynAct Pharma”) today announced that the company has decided to adapt the clinical development programme for the candidate drug AP1189 based on new results from the first multiple-dose cohort in the ongoing Phase I study. The experimental tablet formulation used has been shown to result in excessively variable plasma concentrations. The company has therefore decided to return to the previously used suspension formulation of AP1189 which previously showed more stable pharmacokinetics and promising plasma concentrations for the remainder of the Phase I study. At the same time, development of an improved oral formulation has been initiated for use in future phase II studies. This is expected to lead to delay the planned start of a Phase II study in patients with active arthritis by 12 months.
As previously announced, a suspension of AP1189 in the initial part (single dose) of an ongoing Phase I study has shown good results regarding both safety and tolerability in single doses, which exceed the doses expected to give therapeutic effect by a good margin. The pharmacokinetic properties also provide support for the substance to be administered as a tablet once a day.
In the second part of the study (repeated dosing), a total of 12 healthy subjects have now been dosed with either an experimental tablet formulation of AP1189 (200 mg) or placebo once daily for 14 days. Based on a review of the data, the study’s safety committee has determined that AP1189 is well tolerated and exhibits a good safety profile at dosage in this way. However, the pharmacokinetic analysis shows that the experimental tablet formulation is not suitable for continued development due to excessive variability in measured plasma concentrations. Therefore, SynAct Pharma has decided not to carry out the planned remaining higher dose cohorts in the second part of the study with the current tablet formulation. Instead, the company intends to use the suspension which previously showed stable pharmacokinetics with low variability in plasma concentrations for further evaluation. This allows for optimum continuation of the evaluation of AP1189 for safety and tolerability at dosing for 14 days, which is also the main purpose of the study. Since the change in the study plan requires certain additional documentation, which in turn will be approved by the Ethics Committee and the Pharmaceutical Agency, the phase I programme is expected to be completed around the end of 2018/19 and not during the middle of the year as previously communicated. The company will also promptly initiate the development of an improved oral formulation for use in future phase II studies. Overall, this means that the timetable for the planned Phase II study in patients with active arthritis is delayed and that the study will be initiated when an oral formulation suitable for patient studies is available. This is expected to be available in 2019. SynAct Pharma has a stable financial situation with cash funds which, assuming the successful development of an improved oral formulation, as well as the necessary internal reprioritisation, are expected to be sufficient to implement the planned Phase II study.
CEO Jeppe Øvlesen comments
“We are of course disappointed that the experimental tablet formulation has not proved to meet our high standards, and we are now taking the necessary steps to minimise the delay in the continued clinical development of our unique pharmaceutical programmes, which, in preclinical development and in the single-dose part of the ongoing Phase I study, showed good results regarding both safety, tolerability and pharmacokinetics with promising plasma concentration”.
This is information that SynAct Pharma AB is obliged to disclose under the EU’s market abuse regulation. The information was submitted by the above contact person for publication on 12th June 2018.
For further information about SynAct Pharma AB, please contact:
CEO, SynAct Pharma AB
Telephone: +45 28 44 75 67
CSO, SynAct Pharma AB
Telephone: +45 40 15 66 69