AbbVie 3Q13 – No diabetic nephropathy updates; atrasentan remains in ongoing phase 3 SONAR Trial – October 28, 2013

AbbVie reported 3Q13 financial results in a call led by CEO Richard Gonzalez Friday morning. Management provided no updates to AbbVie's phase 3 diabetic nephropathy candidate, atrasentan (ABT-627). As a reminder, atrasentan is an endothelin-receptor antagonist and began its phase 3 SONAR trial in May 2013. The trial’s primary completion date is estimated to be February 2017, suggesting that the earliest it could come to market would be 2018. Management noted that SONAR would serve as the single global registration trial for the compound. According to ClinicalTrials.gov (Identifier: NCT01858532), SONAR’s primary endpoint is time to first occurrence of a component of the composite renal endpoint: doubling of serum creatinine (confirmed by a 30-day serum creatinine) or the onset of end stage renal disease (needing chronic dialysis, renal transplantation, or renal death). Secondary endpoints include measures of albuminuria, estimated glomerular filtration rate (eGFR), and cardiovascular outcomes. The study will enroll an estimated 4,418 people with type 2 diabetes and nephropathy treated on maximum tolerated doses of an ACE inhibitor or ARB. People with eGFR between 25 and 75 ml/min/1.73 m² may enroll (stage 2-4 chronic kidney disease [CKD]), and the number of people with eGFR between 60 and 75 ml/min/1.73 m² (stage 2 CKD) will be limited to 10% of the population. This represents a broader patient population than bardoxolone methyl’s BEACON trial (which was terminated in October 2012 due to excess mortality and serious adverse events and enrolled only very high-risk patients [stage 4 CKD; see http://close.cx/BEACON] for more details). Of course, this is the population that needs the most help, but also the group of patients that is the most fragile – we hope that AbbVie’s broader approach to enrolling SONAR may allow for subgroup analyses if a safety signal appears again in the very-advanced CKD population. This hard outcomes trial should provide clarity on the benefits to renal function suggested by short-term phase 2 data (which only measured changes in albuminuria [protein in the urine], a proxy for renal impairment, and not hard renal outcomes). The trial’s ClinicalTrials.gov listing does not specify which dose AbbVie carried forward to phase 3.

There was no kidney-related Q&A.

• Phase 2b data for atrasentan were presented at the European Renal Association-European Dialysis and Transplant Association Congress in May – atrasentan provided significant reductions in albuminuria in people with type 2 diabetes and nephropathy who were already receiving maximum tolerated doses of an ACE inhibitor or ARB (the current standard of care for blood-pressure-lowering). Please see our AbbVie 2Q13 report at http://close.cx/AbbVie2Q13 for more details.
• Certainly, the need for CKD treatments is great; currently available treatments can slow the course of disease, but cannot reverse it. The CDC estimates that 35% of adults with diabetes have CKD. Diabetic kidney disease accounts for 40% of new cases of end-stage renal disease (ESRD), and over 100,000 patients a year progress from CKD to ESRD. Effective therapies for diabetic nephropathy are especially valuable since diabetes is the leading cause of kidney failure, and the annual cost of treating ESRD was $42.5 billion in 2009 according to the NIDDK.
• Lilly, Pfizer, Concert Pharmaceuticals, and Vascular Pharma are also investigating treatments for diabetic nephropathy in phases 1 and 2.
  
  • Concert Pharmaceuticals’ candidate (CTP-499) is in phase 2; primary completion is expected July 2013, putting CTP-499 behind atrasentan. According to Concert, CTP-499 is an inhibitor of inflammation, oxidation, and fibrosis meant to be used in adjunct to current standard CKD therapies such as ACE inhibitors or ARBs. Concert recently received patent protection for CTP-499 – details on this update can be found at http://www.closeconcerns.com/knowledgebase/r/d7d781df. More background on CTP-499 can be found in our April 13, 2013 Closer Look at https://closeconcerns.box.com/files/0/f/207540711/1/f_2020038350.
  • Lilly has one undisclosed phase 1 small molecule candidate and three phase 2 candidates: LY2623091, a mineralocorticoid receptor antagonist; LY2382770, a TGF-beta monoclonal antibody; and LY3016859, a TGF-alpha/epiregulin monocolonal antibody (an inhibitor of two epidermal growth factor receptor ligands).
  • Pfizer has a phosphodiesterase inhibitor in phase 2 (PF-00489791). Management has previously guided for data disclosure in 2013, and in 2Q13 remarked that data are “forthcoming.”
  • Vascular Pharma is advancing its preclinical diabetic nephropathy candidate, VPI-2690B, into phase 2 testing with funds secured through the company’s Series A round of financing; the company expects to file for investigational new drug (IND) approval in 2H13. Vascular Pharma also announced a deal that gives Janssen Biotech, a subsidiary of J&J, exclusive rights to acquire the company pending trial results. Additional discussion on Vascular Pharma is available in our September 27, 2012 Closer Look at http://www.closeconcerns.com/knowledgebase/r/e3c2a11e.

--by Jessica Dong and Kelly Close