Atacicept

Atacicept is a recombinant fusion protein that contains the soluble TACI receptor that binds to the cytokines BLyS and APRIL. These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases such as IgA Nephropathy (IgAN) and lupus nephritis (LN). Blocking these cytokines with atacicept has been shown in clinical trials to reduce disease causing antibodies.

Vera holds an exclusive worldwide license for the development and commercialization of atacicept in all indications from Merck KGaA, Darmstadt, Germany, a leading science and technology company.

IgAN, also known as Berger’s disease, is an autoimmune disease driven by the deposition of abnormal immune complexes that accumulate in the kidneys, causing inflammatory tissue damage and kidney failure.

LN is a severe renal manifestation of systemic lupus erythematosus (SLE). SLE is a chronic and disabling autoimmune disease in which the body’s own immune system attacks itself. When LN is diagnosed in a patient, mortality risk dramatically increases.

BLyS = B lymphocyte stimulator; APRIL = a proliferation-inducing ligand

IgA Nephropathy (IgAN)

IgAN is a rare but devastating disease and is a common cause of kidney disease, behind chronic hypertension and diabetes.

Up to 50% of IgAN patients progress to end-stage renal disease, requiring dialysis or kidney transplant.

Current standard of care includes angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs), which provide limited clinical benefits with known safety and toxicity issues.

There is a high unmet medical need for safe and effective new medications to treat IgAN.

Target the Source:

Hover over the pathway below to see how Atacicept acts on IgAN Pathophysiology

Atacicept blocks BLyS, a factor important for B cell survival and maturation, resulting in reduced numbers of disease-causing B cells.

Atacicept blocks APRIL, a factor important for Plasma cell survival, resulting in reduced numbers of disease-causing Plasma cells.

Reductions in Plasma cells and in antibody class switching to IgA reduces production of pathogenic Gd-IgA.

Reductions in B cells, Plasma cells, and Gd-IgA work together to cause a reduction in production of Autoantibodies to Gd-IgA.

Therefore, formation of immune complexes is greatly reduced.

This in turn, reduces immune complex deposition in glomeruli and reduces complement activation.

Ultimately, progressive renal injury is reduced.

Atacicept:

A novel biologic investigational therapeutic that is a dual inhibitor of BLyS and APRIL, which targets B cells and plasma cells, and reduces disease causing autoantibodies
Self-administered once weekly by sub-cutaneous injection
Uniquely able to substantially reduce galactose deficient-IgA1 (Gd-IgA1), the core of the immune complexes that cause disease progression and mortality in IgAN patients
Well-tolerated safety profile in clinical studies of >1,000 patients with autoimmune disease

Clinical Data

The molecule Gd-IgA1 is the core of the immune complexes that cause disease progression and mortality in IgAN patients. High serum Gd-1gA1 levels are highly associated with poor renal outcomes in IgAN.

The Phase 2a JANUS study conducted by Merck KGaA evaluated the efficacy and safety of atacicept in IgA nephropathy. Atacicept demonstrated a 60% reduction in Gd-IgA1, becoming the first molecule to achieve a reduction of this magnitude.

Chen P. et al. CJASN 2019; Suzuki Y et al. Clin Exp Nephrol. 2014; Yanagawa H PLoS One 2014; Zhao N et al. Kidney Int 2012; Berthoux F et al. J Am Soc Nephrol 2012; Camilla R et al. Clin J Am Soc Nephrol. 2011; Schena FP et al. Clin Exp Immunol 1989; Czerinsky C et al. J Clin Invest 1986; Coppo R et al. Clin Exp Immunol 1984