Antisense Therapeutics Limited ("ANP" or "the Company") is pleased to advise that positive results have been achieved from the interim analysis of a subset of available data from its Phase II clinical trial of ATL1103 in patients with the growth disorder, acromegaly.
The interim analysis was undertaken on the 8 patients who have completed the full 3 months of dosing at both dosing levels employed in the study. 4 patients received 200 mg of ATL1103 once per week and 4 received the higher dose of 200 mg twice per week (400 mg).
The interim analysis assessed the change (percentage reduction) from each patient's baseline (start of the study) serum Insulin-like Growth Factor-I (sIGF-I) levels to their levels after the completion of dosing with ATL1103. Reducing sIGF-I levels is the primary marker of ATL1103 activity in this trial as acromegaly patients have elevated sIGF-I levels compared to the normal population and furthermore, reduction of sIGF-I to within the normal range in a significant proportion of patients is the goal in Phase III registration trials for acromegaly treatments.
In the 4 patients who received the 400 mg per week dose, ATL1103 reduced sIGF-I levels consistently and by an average (mean) of 30% (range 4% to 48%) at week 14 (one week past the last dose) which is the primary efficacy time point for the trial. sIGF-I levels were reduced by a mean of 38% (28 – 48%) in the 3 patients who had lower body weights (58 - 83 kg at screening) and thereby received a relatively higher dose per kg bodyweight. The one patient showing the lowest sIGF-1 reduction at week 14 had the highest body weight (132 kg at screening).
At the 200 mg per week dose, no consistent reduction in mean sIGF-I levels was observed at week 14, although some sIGF-I reduction was noted in individual patients.
The time course data (see Figure 1) at the 400 mg per week dose generally shows a progressive rate of reduction in sIGF-I over the dosing period. This is further support for the therapeutic action of ATL1103 observed in this trial and suggests that continued dosing of ATL1103 at the 400 mg per week dose for longer than 3 months could result in additional reductions in sIGF-I.
While sIGF-I levels were substantially suppressed in 3 patients receiving the 400 mg per week dose of ATL1103, their sIGF-I levels did not reduce all the way to normal levels, however this is not surprising considering the study design was not optimised for this endpoint, the small number of patients analysed thus far and that their starting sIGF-I levels (2.4 to 5 times above normal) appear higher when compared to average starting levels of acromegaly patients in larger published clinical studies (e.g. 1.8 times above normal).
To date no patients dosed with ATL1103 have withdrawn from the study nor have any serious adverse events, believed to be treatment-related, been reported. So far, both doses appear to be well tolerated. The positive safety profile to date suggests the drug may be tolerated at higher levels than 400 mg per week and so the Company is considering the prospect of conducting a small add-on study to support the use of a higher dose in Phase III trials for dose escalation in patients with more active disease.