Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial

Abstract

ObjectivesTo evaluate treatment with the peptide-based agent, Lupuzor, in a double-blind, randomised, placebo-controlled study of patients with systemic lupus erythematosus.MethodsPatients who met ≥4 of the American College of Rheumatology criteria, had a score of ≥6 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and did not have an A score on the British Isles Lupus Assessment Group (BILAG)-2004 scale were eligible. 149 intention-to-treat (ITT) patients were randomly assigned to receive Lupuzor (200 μg) subcutaneously every 4 weeks (n=49; group 1) or every 2 weeks (n=51; group 2) or placebo (n=49; group 3) in addition to standard of care (SOC). A target population (136 ITT patients) consisting of patients having a clinical SLEDAI score ≥6 at week 0 was considered. The clinical SLEDAI score is the SLEDAI-2K score obtained by omitting low complement and increased DNA binding components.ResultsIn the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in group 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index (SRI) response at week 12. In the target population, the results were more impressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in the placebo group achieved an SRI response at week 12. An interim analysis including 114 patients from the target population demonstrated an even better efficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs 41.5% (p<0.025) at week 12 and 84.2% vs 45.8% (p<0.025) at week 24). The most common adverse event was a mild injection-site erythema.ConclusionsLupuzor/200 µg given three times at 4-week intervals during 12 weeks in addition to SOC is efficacious and generally well tolerated.

Upcoming biological therapies in systemic lupus erythematosus

“…Similar results were obtained in a subsequent Phase IIb randomized placebo-controlled trial involving 136 SLE patients, showing a a significantly higher SRI than placebo at week 12 (62 vs 39%) [36]. Further studies are currently ongoing.…”

Pharmacological regulators of autophagy and their link with modulators of lupus disease

“…P140 also reduces autophagic flux in MRL/lpr B cells treated in vitro (Page et al, 2011). In a multicenter, randomized, placebocontrolled phase IIb study, P140/lupuzor was found to be safe and met its primary efficacy end points in lupus patients (Zimmer et al, 2013).Other low MW compounds target lysosomes and therefore affect the autophagic flux and as a consequence the autophagosome-lysosome fusion (see below). The two wellknown members of this family of molecules are chloroquine (CQ) and HCQ, which are widely used for the prophylactic treatment of malaria.…”

T Cell Targeted Therapies in Lupus: Do They Make Sense?

“…The response rate using the SLE responder index (SRI) was 53.1 % in forigerimodtreated patients at 12 weeks versus 36.2 % in the placebo arm (p=0.048). In a sub-analysis restricted to patients with more active disease at entry (defined by SLEDAI score ≥6), the response rate using SRI increased to 61.9 % in the treatment versus 38.6 % in the placebo group (p=0.016) [57]. The drug is currently in phase III development.…”

“…In a randomized, controlled trial of 149 South American patients with SLE active on standard of care treatment, forigerimod was well tolerated and more effective than placebo [57]. The response rate using the SLE responder index (SRI) was 53.1 % in forigerimodtreated patients at 12 weeks versus 36.2 % in the placebo arm (p=0.048).…”