Positive Results of Phase 2b Clinical Trial of Pharmalink's Nefecon in Primary IgA Nephropathy Published in The Lancet

STOCKHOLM, March 29, 2017 /PRNewswire/ --

Pharmalink AB, a specialty pharma company, announces that positive results and analyses from the completed Phase 2b trial of its oral drug candidate Nefecon® in primary IgA nephropathy (IgAN) patients have been published online in The Lancet (Fellström et al, reference below). This is the first time the full results from this trial have been published in this format.

In the paper, clinical data are presented that demonstrate the clear potential of Nefecon, a novel, targeted-release formulation of the corticosteroid budesonide, as a new treatment for patients with primary IgAN (a progressive inflammatory kidney disease). More specifically, the trial (known as the NEFIGAN Trial) met its primary endpoint and concluded that the use of Nefecon, in addition to standardized rigorous blood pressure control (optimized RAS blockade), reduced proteinuria and stabilized estimated glomerular filtration rate (eGFR) in patients at risk of developing end-stage renal disease (ESRD). Both of these effects are indicative of a reduced risk of future progression to ESRD.

Pharmalink is preparing to start pivotal Phase 3 studies of Nefecon in this indication.

Johan Häggblad, CEO of Pharmalink, said: "We are delighted with the results from the NEFIGAN Trial that have been published in the prestigious Lancet journal. These results have encouraged us in our considerations and preparations for a pivotal Phase 3 registration trial of Nefecon in primary IgAN patients. We thank all the investigators and patients who contributed to this clinical trial and look forward to advancing our clinical development plans with this exciting drug candidate."

"These clinical trial results strongly support the concept of targeting the gut immune system in primary IgAN patients with persistent proteinuria. Furthermore, they confirm the potential of Nefecon to become the first disease-specific treatment for primary IgAN, with a risk-benefit profile supportive of its use early in the course of disease," commented Bengt Fellström, MD, PhD, Professor of Nephrology at Uppsala University Hospital and Principal Investigator of the NEFIGAN Trial. "IgA nephropathy is the most common inflammatory kidney disease and in real need of new treatment options that prevent or delay patients progressing to renal failure, which has a devastating impact of patients' quality of life. A new medicine with the potential to stop or delay disease progression, and minimize any further loss of renal function, thereby reducing the requirement for dialysis or kidney transplantation, would be very welcome news to patients and clinicians."

The primary outcome of the Phase 2b clinical trial was assessed on the full analysis set (n=149), defined as all randomized patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement (modified intention-to-treat analysis). At nine months, mean urine protein creatinine ratio (UPCR) decreased by -26.4% with Nefecon [p=0.0066] (-29.3% with 16 mg/day [p=0.009], non-significant -23.7% with 8 mg/day [p=0.029]), vs. placebo. The effect was sustained throughout follow-up; mean UPCR decreased by -32% from baseline at 12 months for 16 mg/day vs. a 0.5% increase for placebo. Over nine months, eGFR was stable with Nefecon but decreased 9.8% with placebo (Nefecon vs. placebo: p=0.001). Nefecon was well tolerated and the total incidence of treatment-emergent adverse events was similar across all treatment groups.

Reference 

Fellstrӧm, BC, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomized, placebo-controlled phase 2b trial (2017) The Lancet, http://dx.doi.org/10.1016/S0140-6736(17)30550-0

About the NEFIGAN trial 

The NEFIGAN trial was randomized, double-blinded, and placebo-controlled in male and female patients (aged ≥18 years) with primary IgAN and overt proteinuria considered at risk of progressing to end-stage renal disease (ESRD). The trial was conducted at 62 sites across 10 European countries between November 2012 and June 2015. Data from 149 patients constituted the final analysis set, from a total of 249 patients screened.

Following a 6-month run-in phase (to optimize RAS blockade treatment), patients underwent a 9-month treatment phase in which they were randomized in a 1:1:1 ratio to receive Nefecon at 16 mg/day, 8 mg/day or placebo.

The primary outcome was mean change from baseline in urine protein creatinine ratio (UPCR) over the 9-month treatment phase. The primary analysis compared mean change from baseline in UPCR at 9 months between Nefecon-treated patients (16 mg/day and 8 mg/day combined) and placebo-treated patients. Key secondary and tertiary outcomes, assessed at various time points, included mean changes from baseline in eGFR as well as other measures of urine protein content.

About IgA Nephropathy 

IgA nephropathy (IgAN) is the most common form of glomerulonephritis (inflammation of the kidney glomeruli). The disease is characterized by deposits, predominantly containing polymeric IgA antibody, in the kidney that cause inflammation and renal damage.

IgAN can occur at any age, but the clinical onset is commonly during the second or third decades of life. It has been estimated that up to 40% of patients with primary IgAN progress to renal failure, often referred to as ESRD within 5-30 years following diagnosis. This patient population is estimated to at least 200,000 in major markets.

Patients suffering renal failure require dialysis or kidney transplantation. Primary IgAN accounts for 10% of renal transplants among patients with primary glomerulonephritis in the US and between 7-20% of patients in Europe and Australia in long-term dialysis and renal transplantation programs.

About Nefecon® 

Nefecon is an investigational treatment for patients with primary IgA nephropathy (primary IgAN) at risk of developing ESRD. Nefecon has successfully completed a randomized, placebo-controlled Phase 2b study in 149 primary IgAN patients (full analysis set) at risk of developing ESRD, under standardized rigorous blood pressure control with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB). A Phase 3 registration trial is being planned.

Nefecon is an oral, targeted-release and locally acting formulation of the potent corticosteroid, budesonide, that down-regulates the disease process in the kidney through suppression of the gastrointestinal immune system thus exploiting the pivotal role the gastrointestinal tract plays in the overall immune response. Promising results indicate that treatment with Nefecon may provide clinical benefits to primary IgAN patients at risk of progressing to ESRD, and provide an alternative to dialysis and transplantation. Nefecon has received orphan drug designation in primary IgAN by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

About Pharmalink AB 

Pharmalink is a specialty pharma company developing high value products for patients with significant unmet medical needs. With a highly experienced, dynamic management team, Pharmalink draws on its extensive experience of pharmaceutical development and marketing to efficiently identify and progress valuable and de-risked products.

Visit http://www.pharmalink.se for further information.