AbbVie Inc. announced the initiation of a Phase 3 clinical study called SONAR (Study Of Diabetic Nephropathy with Atrasentan) to assess the effects of the investigational compound atrasentan - when added to standard of care - on progression of kidney disease in patients with stage 2 to 4 chronic kidney disease (CKD) and type 2 diabetes. SONAR is a large, multinational, double-blind, placebo-controlled clinical study that is expected to enroll more than 4,000 patients with diabetic nephropathy. The study will evaluate atrasentan's impact on renal outcomes, such as the onset of end-stage renal disease (ESRD), as defined by need for chronic dialysis, transplant or death due to renal failure progression. The initiation of the Phase 3 study follows results from Phase 2b studies. Diabetic nephropathy, or diabetic kidney disease, is a common complication of diabetes and the leading cause of CKD in the developed world. In the US, approximately 40% of patients with diabetes develop diabetic nephropathy. Albuminuria - protein in the urine, as measured by urine albumin-to-creatinine ratio (UACR) - is the main sign of diabetic nephropathy. As kidney function decreases, the level of protein in the urine rises, leading to further damage to the kidney. Previous research has suggested that endothelin receptors play a role in this process and drugs that target this receptor system, such as atrasentan, may have the potential to delay progression of CKD. Phase 2b Studies: the Phase 2b studies of atrasentan were conducted to evaluate the efficacy and safety of atrasentan in lowering albuminuria in subjects with type 2 diabetes and nephropathy receiving maximum tolerated labeled doses of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB). Two parallel, double-blind, placebo-controlled, multinational studies were conducted: one in Japan with 58 patients and a second in the US, Canada and Taiwan with 153 patients. Findings from the 12-week studies of two doses of atrasentan (0.75 mg, n=78; 1.25 mg, n=83) vs. placebo (n=50) showed sustained reductions in UACR (primary endpoint): 36% in the 0.75 mg, 44% in 1.25 mg group vs. increase of 2% in placebo group (P<0.001). Additionally, as secondary endpoints: a more than 30% albuminuria reduction was observed in 51% and 55% of the atrasentan subjects, respectively (P=0.001). Changes in estimated glomerular filtration rate (eGFR), another important measure of kidney function, were measured compared to placebo in both groups (0.75mg= -0.81/min/1.73m2; p=0.412 and 1.25mg= -0.91 ml/min/1.73m2; p=0.355), and did not change significantly compared to placebo. In the Phase 2b studies, the observed adverse events were similar among the three treatment and placebo groups. The most commonly observed adverse events included peripheral edema (35% in 0.75mg arm, 42% in 1.25 mg arm vs. 42% on placebo), diarrhea and constipation (13% in 0.75mg arm, 21% in 1.25 mg arm vs. 14% on placebo). There were no significant differences in the rate of peripheral edema or diarrhea and constipation among the treatment and placebo arms. A small% age of subjects discontinued the study due to adverse events (8% on 0.75 mg, 15% on 1.25mg vs. 0 on placebo), with edema as the most commonly cited reason. Importantly, the study concluded that the 0.75 mg dose of atrasentan administered orally once daily showed the best efficacy-safety balance, informing the dosing of atrasentan selected for further investigation in the Phase 3 clinical study. SONAR is a randomized, double-blind, parallel, placebo-controlled, multicenter study designed to assess the effects of atrasentan (0.75 mg administered orally once a day) on renal outcomes in patients with type 2 diabetic nephropathy (diabetic kidney disease) while they continue to be treated with the current standard of care: the maximum tolerated labeled daily dose of a RAS inhibitor, such as an ACE inhibitor or an ARB, and a diuretic. Inclusion criteria for patients includes estimated GFR (another important indicator of kidney disease progression) of 25 to 75 mL/min/1.73 m(2), UACR >300 and <5,000 mg/g, and systolic blood pressure within 110 and 160 mgHg. The primary endpoint will evaluate the effect of atrasentan on time to doubling of serum creatinine or the onset of ESRD, as defined by need for chronic dialysis, transplant or death due to renal failure. Secondary endpoints will assess the effects of atrasentan on urine albumin excretion, eGFR and cardiovascular events including cardiovascular death, heart attack and stroke. Quality of life evaluations also will be conducted. After initial screening, patients will be enrolled in a run-in period to optimize RAS inhibitor and diuretic doses. Eligible patients will then enter an enrichment period, in which they will receive atrasentan 0.75 mg/day for six weeks to determine their UACR response and to assess tolerability of atrasentan. Approximately 3,150 responders (UACR reduction > 30% from baseline) and approximately 1,000 non-responders (UACR < 30% reduction from baseline) will then be randomized 1:1 into a double-blind treatment period, which will continue for approximately 48 months.

Galapagos NV and AbbVie Inc. announced an extension of their GLPG0634 clinical development collaboration to include Crohn's disease. Galapagos will fund and complete a Phase 2 program in Crohn's disease, which is designed to facilitate rapid progression into Phase 3. Upon successful completion of the study, expected in second quarter of 2015, AbbVie will pay Galapagos $50 million. The terms of the collaboration extension are in addition to previously agreed upon financial terms. AbbVie will be responsible for funding and performing clinical development beyond Phase 2, and completing regulatory and commercialization activities. Galapagos will start an innovative 20-week, Phase 2A/B study with GLPG0634 in 180 patients suffering from Crohn's disease by early 2014. The study will measure both induction of disease remission and early maintenance of its beneficial effects in Crohn's disease, and is expected to read out topline results in second quarter of 2015. This Phase 2 study in Crohn's disease will be performed in parallel with the Phase 2B study in rheumatoid arthritis (RA). Crohn's disease is a serious chronic, inflammatory autoimmune disease of the gastrointestinal (GI) tract that affects millions of people worldwide, including more than one million people in Europe and more than 500,000 people in the U.S. The Janus kinases (JAK) are a family of enzymes that play a key role in the signaling mechanism used by a number of cytokines that are involved in autoimmune diseases. JAK inhibitors, with their immune-modulating effects, have the potential to become an effective treatment option for this disease. By inhibiting JAK1, GLPG0634 blocks signaling for several key pro-inflammatory cytokines such as interleukin 6 (IL-6). Its selective JAK1 inhibition profile avoids inhibition of JAK2 which offers a unique advantage in Crohn's disease. Inhibition of JAK2 has shown anemia and reduced formation of blood cells in clinical studies with other JAK inhibitors, which is a particular concern in patients with inflammatory bowel disease, as blood loss through gastrointestinal bleeding often already causes anemia in these patients. Therefore, GLPG0634 may potentially support a better safety profile than other JAK inhibitors.

AbbVie Inc. ratified the appointment of Ernst & Young LLP as auditors at its AGM held on May 6, 2013.