ImmuPharma PLC announced the final results from a Phase IIb trial of LUPUZOR™ in active patients with Systemic Lupus Erythematosus (SLE). Lupuzor™ administered at 200 mcg once-a-month for 3 months plus standard of care achieved a clinically significant improvement in patient response rate as measured by the combined score compared to placebo plus standard of care. The study results also show that Lupuzor™ was generally well tolerated, with adverse event rates lower with Lupuzor™ when compared to placebo.


- Lupuzor™ achieved a clinically significant improvement in patient response rate versus placebo in the intention to treat (ITT) analysis

- The improvement was statistically significant in a subgroup (90% of the ITT population) of moderate to severe patients
- 62% of this sub-group of patients were responders according to both a composite clinical score and a decrease of 4 points of the SLEDAI score when treated with Lupuzor™ 200 µg every 4 weeks for 12 weeks compared to 41% on placebo

- Lupuzor™ was generally well tolerated with fewer serious AEs leading to discontinuation

Details of the Phase IIb study with Lupuzor™

This phase IIb study was a randomized, double-blind placebo controlled, dose-ranging study in 150 (initially planned 204) patients designed to evaluate the efficacy of Lupuzor™ in a three-month treatment period of either subcutaneous (SC) injection of 200 mcg once-a-month (4qw) or 200 mcg twice-a-month (2qw) or placebo in addition to standard of care and followed by a 3 month follow-up period.

The primary efficacy endpoint of the study was based on the combined score, which is defined by: (1) a reduction from baseline of at least 4 points on the 2K-SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician's Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); and (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which indicates a moderate flare of disease activity). An additional end-point was the response rate based only on the decrease of the SLEDAI score by 4 points.

An interim analysis was performed and included 125 patients out of the ITT population having completed by mid November 2008 the week 12 assessments, approximately half of them having also completed the 12 week follow-up period. These results were announced in January 2009 indicating that Lupuzor™ administered at a 200 mcg dose once-a month for 3 months was statistically significantly superior to placebo, using a decrease of 4 points of the SLEDAI score to define a responder with drop-outs being considered according to the protocol as non-responders. As the study showed a statistically significant improvement even with a much lower number of patients, ImmuPharma decided to stop the recruitment of further patients. All patients already recruited completed the study according to protocol.

The study was planned to originally enroll any patient with SLEDAI ≥ 6. Soon after study commencement the protocol was formally amended to ensure only patients with a clinical SLEDAI ≥ 6 (defined as the moderate to severe subgroup) were included.

The study was terminated with an ITT population of 147 patients (Intent To Treat population) and the moderate to severe subgroup of 134 patients (90% of the ITT population) in line with the amended protocol.

Key findings from the Phase IIb study with Lupuzor™

The analysis of the study revealed for Week 12:

1) ITT population:

a) Primary endpoint (Combined score responders): Lupuzor™ once-a-month 53% (p = 0.048). Lupuzor™ twice-a-month: 45%; placebo 36%

b) SLEDAI score responders: Lupuzor™ once-a-month 53% (p = 0.073). Lupuzor™ twice-a-month: 45%; placebo 38%

2) Moderate to severe subgroup Population Week 12 a) Primary endpoints (Combined score responders): Lupuzor™ once-a-month 62% (p = 0.016). Lupuzor™ twice-a-month: 48%; placebo 39%

b) SLEDAI score responders: Lupuzor™ once-a-month 62% (p = 0.026). Lupuzor™ twice-a-month: 48%; placebo 41%

All treatments (Lupuzor™ or placebo) were administered in addition of standard of care which may include patients on low dose steroids (< 80mg prednisone/week). 200 µg of Lupuzor™ administered once-a-month during 3 months (total 600 µg) achieved a clinically and statistically meaningful improvement of the moderate to severe subgroup. An analysis after a further 12 week follow-up (with only standard of care) revealed that the responder rates further increased to reach about 70% in the moderate to severe subgroup compared to 59% on placebo. Lupuzor™ was well tolerated and its safety profile was better than placebo with less drop-outs (1 vs 8) and less serious AEs leading to discontinuation.

Lupus is a disease that involves an inappropriate functioning of the immune system in that the immune-competent T and B cells are generating antibodies against certain self proteins. Lupuzor™ corresponds to the sequence 131-151 of the 70k snRNP protein with a Serine phosphorylated in position 140. It was discovered by France's National Center for Scientific Research (Centre National de la Recherche Scientifique) and further developed by ImmuPharma and is now licensed to Cephalon Inc. Lupuzor™ modulates both the auto-reactive T and B cells involved in Lupus in order to render the functioning of the immune system more appropriate while maintaining its overall efficacy.

Commenting on the detailed results of the study, Dr Robert Zimmer, MD. PhD, ImmuPharma's President and Chief Scientific Officer said: "We are absolutely delighted that Lupuzor™'s phase IIb study has delivered such very encouraging clinical efficacy data reaching statistical significance in the moderate to severe subgroup (90% of the ITT population) and with an overall efficacy peaking at 70%. The information gathered in this study, in addition to the very small number patients needed to prove efficacy, paves the way for a medical and commercial success of Lupuzor™.

Frank Baldino Jr, Ph.D, Cephalon's Chairman & CEO added: "We are pleased to have the opportunity to further develop Lupuzor and potentially bring a new medication to the lupus patients who have waited 50 years for new therapy."

ImmuPharma PLC