Treatment for Lupus (Lupuzor TM)
Background
Lupus is a chronic, potentially life-threatening autoimmune disease. By 2010 there will be an estimated 1.4 million people diagnosed in the seven key markets. 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 or specific treatment.
ImmuPharma's compound
Lupuzor™ (previously known as IPP-201101) 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 is now in preparation for phase III. The Phase IIa study, in Lupus patients 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 3 times by subcutaneous injections 2 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™ on only 3 occasions, 2 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 auto-antibodies and increase in IL-10. Many of the patients that were treated with the drug showed reduction in their auto-antibodies and showed also 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 randomized 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 4 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 these data follows on from the successful results which we saw with the preliminary Phase IIa trial.
Based on this interim analysis, ImmuPharma has discontinued the recruitment of more patients for the Phase IIb study. The 147 patients already randomized will continue the study to completion according to the protocol. A full analysis of the data will be provided in due course.
The latest highlights of Lupuzor's™ development are:
- 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 IMPD (Investigational Medicinal Product Dossier) 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.
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 standardized 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 primary endpoint due to the short treatment period.
ImmuPharma entered into a corporate deal with Cephalon Inc in November 2008 whereby Cephalon licensed worldwide the exclusive rights to Lupuzor.
Cephalon became subject to a takeover bid by Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) and in July 2011, Cephalon announced that its stockholders voted to approve the Teva proposal to acquire Cephalon for $81.50 per share in cash, or a total enterprise value of approximately $6.8 billion.
The transaction became effective on October 14, 2011. Due to the acquisition of Cephalon by Teva, ImmuPharma regained all rights to Lupuzor worldwide and initiated discussions with other pharmaceutical companies for a corporate deal on Lupuzor™.
