Clinical Phase I & II Summary

Overview

In WILEX’s Phase I & II clinical development programme, which has been completed already, more than 130 patients with metastatic ccRCC were treated with RENCAREX®. The programme included three Phase l studies to examine pharmacokinetics, biodistribution and safety. In addition, three Phase ll efficacy studies have been completed, one study with RENCAREX® as monotherapy and two combination studies with RENCAREX® plus low-doses of the cytokines Interleukin-2 (IL-2) or Interferon-alpha (IFN alpha-2a). In all studies RENCAREX® was well-tolerated with no serious drug related side effects. In addition to being safe and well-tolerated RENCAREX® demonstrated a promising efficacy profile. Follow-up observation for long-term survival of patients enrolled in the Phase II showed a positive effect on median survival.

RENCAREX® (WX-G250) has shown excellent safety and tolerability in over 130 patients evaluated in clinical phase I and II trials. No serious drug related side effects were seen. RENCAREX® showed excellent binding to RCC tumour tissue and metastases in patients. In a clinical phase I study with the antibody trace labelled with 131-Iodine, all known metastases were detected in patients (see image).

Fig.: Whole body radioimmunoscintigrams using the 131-Iodine labelled WX-G250-antibody for imaging showing a renal cancer patient with metastases at various sites. The G250 antibody shows excellent localisation in renal tumours. Radioimmunoscintigrams courtesy of Prof. F.H.M. Corstens, University of Nijmegen, Netherlands.

Promising Efficacy in Phase II Studies

RENCAREX® has shown a promising efficacy profile in three phase II efficacy studies in patients with stage 4 metastatic RCC. One study was carried out with RENCAREX® in monotherapy, two studies were conducted with RENCAREX® in combination with low-dose Interleukin-2 or Interferon-alpha-2a respectively.

Taking the RENCAREX® results as a whole, over 30% of patients derived clinical benefit from the treatment they received. In particular, RENCAREX® treatment has significantly increased median survival rates in this difficult to treat population.

In a European Phase II multi-centre monotherapy study 36 patients with stage 4 metastatic clear cell RCC were treated over the period of eight weeks with 50 mg weekly RENCAREX®. Patients were stratified into two groups. Those patients who showed a clinical benefit (defined as a response to treatment and/or stabilisation of previously progressive disease) after 12 weeks of treatment had the option to receive further 8 weeks of treatment with RENCAREX® (“Extended Group”), whereas patients who did not show clinical benefit discontinued treatment (“Discontinued Group”).

Results: Patients with extended treatment had significantly longer survival (median survival 39 months, 2-year survival rate 70%) compared to patients in the discontinued treatment group (median survival 10 months, 2-year survival rate 26%). There was no difference in the two groups’ patient characteristics. Median survival of all patients in the “Intent To Treat” (ITT) population was 15 months. Overall clinical benefit (defined as an either complete or partial response to treatment and/or stabilisation for more than 6 months of previously progressive disease) had been observed in 28% of evaluable patients, all with progressive metastatic disease at study entry. See figure below.

Fig.: Efficacy results (median survival and 2-year survival) of Phase II monotherapy study with RENCAREX® in patients with metastatic RCC.