Project: Development of PL-56 (Nefecon), a new drug candidate against IgA nephropathy.
AIM_x000D_The overall plan of this project is to develop and manufacture sufficient quantities of cGMP quality NEFECON study drug to conduct a clinical trial in line with the regulatory guidance and state of the art methodology with the aim to obtain marketing authorisation for its use in patients with primary IgA nephropathy (IgAN). In addition, this project will help elucidate possible mechanisms of action for the causes of and possible treatment of IgAN. _x000D_ _x000D_BACKGROUND_x000D_IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Still, the pathogenesis is not fully established, and it is likely that IgAN is a heterogenic disease. The common pathological features include circulating immune complexes and deposition of IgA1 and complement C3 in the glomerular mesangium. The IgA1 is aberrantly glycosylated, which might facilitate binding to mesangial cells. The deposition of circulating IgA1-immune complexes induces mesangial cell proliferation and release of a number of cytokines and growth factors associated with development and progression of renal injury._x000D_IgAN is considered to be mediated by immune-complexes. However, there are controversies about whether the immune complexes are antigen-antibody dependent or independent. Further, it is not known whether any antigens are exogenous or endogenous. Food antigens have been proposed as being involved in the pathogenesis of IgAN, and gluten has been studied in particular. Studies have shown that experimental IgAN can be induced by gliadin in mice, and an association between IgAN and celiac disease has been reported. Other food antigens have been subject to investigation in IgAN patients as well. If all dietary or gastrointestinal antigens relevant for IgAN development were identified, the optimal therapeutic strategy would be to simply eliminate the antigens. However, as we suspect that a number of antigens might be involved, and not only antigens present in the gastrointestinal tract, the alternative strategy would be to down-regulate the enhanced reactivity and aberrant process of the gastrointestinal immune system. _x000D__x000D_TECHNICAL APPLICATIONS_x000D_The project will consist of three CO subprojects plus an overlying project management component:_x000D_a) Overall consortium management. Months 0-36._x000D_b) Work package 2: Manufacturing to cGMP quality level of PL-56. Months 0-12_x000D_c) Work package 3: Mechanistic studies of NEFECON in primary IgAN. Months 9-36_x000D_d) Work package 4: Clinical trial to confirm efficacy and safety in the target population. Months 9-36_x000D__x000D_MARKET APPLICATIONS_x000D_The immediate target group for Nefecon treatment is estimated to ca 200 000 patients in_x000D_industrialised countries. Patients with chronic renal disease are in frequent contact with a limited_x000D_number of nephrology specialists which are easily targeted by a limited sales force. We are_x000D_calculating with a peak penetration of the primary target group of 12.5%-25% within 10 years postlaunch._x000D_Thus, Nefecon represents a major market opportunity with potential sales exceeding 200_x000D_MUSD per year and a gross margin of 90%. The target group for Nefecon is the approximately 30% of IgA patients with the more aggressive form of the disease and who are at risk of developing end stage renal disease. This patient population is estimated at approximately 200,000 in major markets._x000D__x000D_PROJECT CONSORTIUM_x000D_The Ps are selected based on complementary qualifications. Smerud Medical Research is a Contract Research Organisation with more than 17 years experience in directing and managing clinical research projects, in particular early phase studies or clinical proof-of-concept trials. The Smerud CRO has top level competence in advanced medical statistics, including adaptive design expertise and are responsible for commercialisation (clinical development until marketing authorisation is obtained) of several early phase compounds for the biotech industry. _x000D_Pharmalink is a Swedish specialty pharma company developing high value products for niche indications. Pharmalink draws on its extensive experience of pharmaceutical product development and the excellence of medical science in Sweden to identify and progress products that address significant unmet medical needs. Pharmalink has introduced more than 15 pharmaceutical products to the market._x000D_Professor Bengt Fellström and collaborators from the Renal Unit, Uppsala University Hospital with profound knowledge of nephrology in general, and IgAN in particular are strengthening the consortium as academic consortium Ps.
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Acronym
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SMR-2090
(Reference Number: 6138)
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Duration
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01/02/2011 - 31/01/2014
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Project Topic
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This project is aimed at conducting a pivotal clinical trial demonstrating that PL-56 is an efficient pharmacological alternative to dialysis and transplantation for patients with IgA nephropathy.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 5
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Project partner
