Hope at last! Activity in the Diabetic Nephropathy pipeline

diagnostic form with diabetes writting down with a needle and pills

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

Company/ Product

MOA

Phase III

AbbVie’s atrasentan Endothelin receptor antagonist Ph III (SONAR) initiated 2013 Est. enrollment: 4,148

Timeframe: 48 months

Status: recruiting
Bayer’s finerenone Mineralcorticoid receptor antagonist/ aldosterone antagonist Ph III (FIGARO-DKD, FIDELIO-DKD) initiated Sept-2015 Est. enrollment: 6,400

Timeframe: 36 months

Status: recruiting
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

Status: recruiting
Janssen’s Invokana (canagliflozin) SGLT-2 inhibitor Ph III (CREDENCE) initiated Feb-2014 Est. enrollment: 3,700

Timeframe: 66 months

Status: recruiting

 

Table 1b. Early-Mid Stage Pipeline for Diabetic Nephropathy

Early- Mid Stage Pipeline

Company/ Product

MOA

Clinical Program

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

 

DRG TreatmentTrends® examines the perceptions of nephrologists, endocrinologists, diabetologists, and primary care physicians.

1.USRDS Annual Data Report 2014; http://www.usrds.org/2014/view/Default.aspx

2.Quiroga, B., et al. “Present and Future in the Treatment of Diabetic Kidney Disease.” Journal of Diabetes Research: 1013. Print.

3.DRG PatientBase® report covers the epidemiology of Diabetic Nephropathy forecast over 20 years from 2015-2035.

4.DRG Pharmacor® report forecasts the CKD nondialysis and dialysis markets from 2014- 2024 and provides in-depth coverage of the disease epidemiology, current treatments, emerging therapies, and market outlook. It will publish soon in Q4 2015.