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.

Objective. To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser 140 ), which is recognized by lupus CD4؉ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).Methods. An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor ␣ were measured by ELISA and nephelometry.

Peptides have gained so much attention in the last decade that they are now part of the main strategies, with small molecules and biologics, for developing new medicines. Despite substantial progress, the successful development of peptides as drugs still requires a number of limitations to be addressed, including short in vivo half-lives and poor membrane permeability. Here, we describe the use of oligourea foldamers as tool to improve the pharmaceutical properties of GLP-1, a 31 amino acid peptide hormone involved in metabolism and glycemic control. Our strategy consists in replacing four consecutive amino acids of GLP-1 by three consecutive ureido residues by capitalizing on the structural resemblance of oligourea and α-peptide helices. The efficacy of the approach is demonstrated with three GLP-1-oligourea hybrids showing prolonged activity in vivo. Our findings should enable the use of oligoureas in other peptides to improve their pharmaceutical properties and may provide new therapeutic applications.

This study demonstrates the efficacy of single α-amino acids substitution with ureido residues to design long lasting peptides.