According to primary research conducted by DRG, Diabetic Nephropathy (DN) is considered the nephrology disease with the greatest unmet need for new therapeutic options (TreatmentTrends®: Diabetic Nephropathy (U.S.) 2015 ). DN, also called diabetic kidney disease, is one of many chronic kidney disease (CKD) conditions and is characterized by persistent albuminuria, progressive decline in the glomerular filtration rate, and high blood pressure. While the most common pharmacologic treatments include angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, these treatments cannot reverse DN progression. This is concerning as almost 7 million people in the US have DN and the prevalence is expected to increase by nearly half as many over the next 20 years (PatientBase®: Diabetic Nephropathy 2015 ). This rising prevalence is further exacerbated by the large economic costs associated with CKD. In 2012, Medicare spent over $12.4 billion on CKD patients, representing nearly 20% of Medicare parts A and B spending.2 Policymakers have made efforts to control these costs, such as bundling in the dialysis setting and cost-sharing mechanisms through drug tiers yet these measures can only have a limited effect. Clearly, any agent that can stop or slow the progression of DN would be seen as a major advantage by patients, physicians, and payers.
After notable early pipeline failures and disappointments, the pipeline for DN is now active and growing (Table 1a.). Four novel agents with different mechanisms of action (MOA) are currently enrolling in Phase III testing. These agents are targeting the same population and measure the same primary endpoint but have different trial lengths and sample sizes. In addition to late stage agents, there are several in early-mid stage clinical testing (Table 1b.). Similar to the late-stage pipeline, these agents have different MOAs yet two are mineralcorticoid receptor antagonist/ aldosterone antagonist; this is similar to Bayer’s finerenone. Surveyed physicians weigh in on the most promising MOA in TreatmentTrends®: Diabetic Nephropathy (U.S.) 2015.
DRG has been conducting market research on DN for the past several years to understand the dynamics of this market, the opinions/ behaviors of prescribers, and current treatment strategies. Nephrologists, Endocrinologists, and Primary Care Physicians surveyed by DRG found that their ideal length for a Phase III trial was 2 years or greater.4 In addition, physician perceptions around product development find Janssen’s Invokana to stir the most excitement. TreatmentTrends®: Diabetic Nephropathy (U.S.) 2015 found that more than 65% of surveyed physicians indicated they were highly interested in the product.
This market is poised to rapidly expand over the next several years. Forecasted estimates by DRG have DN agents growing the market and earning upwards of $1 billion in revenue in peak sales (Pharmacor®: CKD (G7) 2015 ). Companies are racing to the finish line with the first disease-modifying agent. The first agent to reach the market will face few competitors and is predicted to be viewed favorably by prescribers given the large unmet need. The current state of the Phase III trials favors atrasentan as the first market entrant, followed by finerenone and Pyridorin. Given the large unmet need, rapidly growing pipeline, and focus on controlling spending within the US healthcare system- DN is a market to watch. Stay tuned for more market research on DN from DRG.
Table 1a. Late Stage Pipeline for Diabetic Nephropathy
|Late Stage Pipeline|| |
|AbbVie’s atrasentan||Endothelin receptor antagonist||Ph III (SONAR) initiated 2013||Est. enrollment: 4,148 |
Timeframe: 48 months
|Bayer’s finerenone||Mineralcorticoid receptor antagonist/ aldosterone antagonist||Ph III (FIGARO-DKD, FIDELIO-DKD) initiated Sept-2015||Est. enrollment: 6,400 |
Timeframe: 36 months
|NephroGenex’s Pyridorin (pyridoxamine dihydrochloride)||Pathogenic oxidative chemistry inhibitor targeting advance glycation endpoint products||Ph III (PIONEER) initiated mid-2014||Est. enrollment: 600 |
Timeframe: 45 months
|Janssen’s Invokana (canagliflozin)||SGLT-2 inhibitor||Ph III (CREDENCE) initiated Feb-2014||Est. enrollment: 3,700 |
Timeframe: 66 months
Table 1b. Early-Mid Stage Pipeline for Diabetic Nephropathy
|Early- Mid Stage Pipeline|| |
|ChemoCentryx’s CCX-140||Chemokine receptor CCR-2 inhibitor||Ph II completed 2014; designing Ph III|
|Noxxon’s ematicap (NOX-E36)||Target CCL-2 chemokine to inhibit pro-inflammatory cells from entering kidney||Ph IIa completed 2013|
|Concert Pharmaceutical’s CTP-499||Multisubtype selective inhibitor of phosphodiesterases (PDEs)||Ph II testing complete; end of phase II meeting with FDA in July 2014.|
|Pfizer’s PF-00489791||PDE-5 inhibitor||Ph II completed 2013|
|Mitsubishi Tanabe’s MT-3995||Mineralcorticoid receptor antagonist/ aldosterone antagonist||Ph II initiated 2015; recruiting in Japan|
|Daiichi-Sankyo/ Exelexis’ CS-3150 (XL550)||Mineralcorticoid receptor antagonist/ aldosterone antagonist||Ph IIb initiated Jan 2015; recruiting in Japan|
1.USRDS Annual Data Report 2014; http://www.usrds.org/2014/view/Default.aspx