Background

Lupus (or Systemic Lupus Erythematosus) is a chronic, potentially life-threatening autoimmune disease. An estimated 1.4 million people are diagnosed in the 7 major world markets (the USA, Japan, Germany, France, Spain, the UK and Italy). Lupus is an inflammatory disease, which attacks multiple organs such as the skin, joints, kidneys, blood cells, heart and lungs. There is currently no cure.

The development of ImmuPharma’s Lupuzor™

ImmuPharma’s compound Lupuzor™ (previously known as IPP-201101 and also referred to as rigerimod or P140) has a novel mechanism of action aimed at modulating the body’s immune system so it does not attack healthy cells, without causing adverse side effects. It has the potential to halt the progression of the disease in a substantial proportion of patients.

Lupuzor™ has successfully completed Phase I, Phase IIa and Phase IIb studies and has now been given the approval by the US FDA to enter Phase III, the final testing phase.

Lupuzor’s™ phase I study which took place in 2006 did not show side effects. The Phase IIa study was run in 2007 in lupus patients and was a proof of concept, dose ranging, safety, multi-centre European study. The proof of concept was assessed by measuring the decrease of anti-dsDNA antibodies as a surrogate marker for efficacy and IL10, a cytokine, to ascertain its mechanism of action. The drug was administered three times by subcutaneous injections two weeks apart at doses of 200 µg and 1000 µg and the patients were monitored one month after treatment stop.

Lupus patients who received Lupuzor™ as a lupus treatment on only three occasions, two weeks apart, demonstrated a significant clinical improvement in their condition in addition to the decrease of their biomarkers.

The Phase IIa trial of Lupuzor™ met its primary end-points. The study was designed to measure biomarkers, including reduction in anti-dsDNA autoantibodies and increase in IL10. Many of the patients that were treated with the drug showed reduction in their autoantibodies and also showed significant improvement in their condition.

A Phase IIb clinical trial started dosing of patients in February 2008 in Europe and Latin America, comparing Lupuzor™ to placebo in patients with systemic lupus erythematosus and an interim analysis has demonstrated statistically significant superiority of Lupuzor™ over placebo. The interim analysis was performed and reviewed by an independent Data Monitoring Committee according to ICH guidelines. This analysis was conducted after 125 randomised patients had completed the 12-week treatment period, half of them having also completed the additional 12-week follow-up (week 24).

The primary efficacy measure was a ‘SLEDAI response’ defined as a decrease of at least four points in the SLEDAI score, a scale generally accepted by physicians as an assessment of the clinical activity of lupus patients, a lower score representing lower disease activity. The analysis of the data has demonstrated that the 200mcg dose of Lupuzor™ administered every four weeks was statistically significantly superior to placebo (p = 0.015). Lupuzor™ was generally well tolerated with no significant drug related adverse events recorded. All this data follows on from the successful results revealed in the preliminary Phase IIa trial.

The latest highlights of Lupuzor’s™ development as a treatment for lupus include:

• An ‘End of Phase 2’ meeting package with ImmuPharma’s Phase IIb data was submitted to the FDA and the FDA responded to all the questions
• The Investigational Medicinal Product Dossier (IMPD) submitted via the Voluntary Harmonized Procedure (VHP) in the EU was approved
• The Scientific Advice meeting with the European Medicines Evaluation Agency (EMEA) was held; the recommendations were very similar to those in the FDA’s ‘End Of Phase 2’ responses. Recommendations were incorporated into the Phase III pivotal programme
• The Japanese equivalent authorities (PMDA) have agreed to the initiation of clinical trials in Japan
• The FDA has granted Lupuzor™ the approval to start Phase III with a Special Protocol Assessment (SPA)
• The FDA has granted Lupuzor™ Fast Track designation
• Most recent development: Landmark collaboration agreement & commencement of Pivotal Phase III Lupuzor™ study with Simbec-Orion
• Registration with the U.S. National Institutes of Health – ClinicalTrials.gov website has now gone ‘live’ confirming Lupuzor’s™ pivotal Phase III trial protocol and the current clinical commencement and completion of the study.  Further details can be viewed at: ClinicalTrials.gov

How Lupuzor™ works in the treatment of lupus

Lupuzor™ is a drug that specifically modulates the immune system of lupus patients by modifying the behaviour of some of the key cells involved in the pathogenesis of the disease. The clinical profile of lupus patients is generally assessed by standardised scales such as SLEDAI (SLE Disease Activity Index): the lower the score, the better the condition of the patient. During this Phase II study, the SLEDAI scores were assessed on multiple occasions even though the study was not designed or powered to demonstrate clinical benefit as the primary endpoint due to the short treatment period.

Corporate deals involving Lupuzor™ 

ImmuPharma entered into a corporate deal with Cephalon, Inc. in November 2008 whereby Cephalon licensed worldwide the exclusive rights to Lupuzor™. Due to the acquisition of Cephalon by Teva on October 14, 2011, ImmuPharma regained all rights to Lupuzor™ worldwide and has initiated discussions with other pharmaceutical companies for a new corporate deal.