Several late-stage renal treatments and market events are set to occur over the next few years, including the potential launch of a new class of renal anemia products, iron-based phosphate binders, and new products for secondary hyperparathyroidism, among others. This should make nephrology an exciting area to study on how nephrologists’ perceptions change over time as new clinical data is released.
In a Q1 2013 data analysis of the options presented to nephrologists describing products in development, nephrologists perceived an oral hypoxia inducible factor-prolyl hydroxylase (HIF-PH) inhibitor to treat anemia to be more valuable to a practice than an iron-based phosphate binder––but less valuable than an oral antioxidant inflammation modulator, which improves GFR (e.g., the method of action of Reata’s bardoxolone). 1
Here is a closer look at physician perceptions of a selection of emerging late-stage treatments.
- FibroGen. This company has a partnership with Astellas Pharmaceuticals on FG-4592/ASP 1517, a HIF-PH inhibitor that is one of many compounds in development to treat renal anemia. This product, like the other HIF-PH inhibitors in trials, works through a different mechanism of action than erythropoiesis-stimulating agents (ESAs). They stabilize HIF, the key regulatory protein that coordinates all elements of erythropoiesis necessary for the formulation of mature red blood cells. In addition, these products down-regulate hepcidin, a regulatory hormone that limits iron availability and thus suppresses erythropoiesis under conditions of inflammation.2
Currently in Phase III development for CKD non-dialysis (CKD-ND) and dialysis patients, FG-4592/ASP 1517 showed a significant increase in hemoglobin (approximately 1 g/dL) in the two highest dose cohorts in its Phase II studies. In addition to potential hemoglobin benefits, HIF-PH inhibitors provide an oral formulation, which may be especially beneficial to patients in the CKD-ND setting where they are seen less frequently by their nephrologists. While our research indicates that surveyed nephrologists have low familiarity with FG-4592/ASP 1517, their interest is high after reviewing a short product description. Furthermore, surveyed nephrologists believe that approximately 40% of CKD-ND and 35% of dialysis patients would be likely candidates for FG-4592/ASP 1517, respectively.
- Akebia Therapeutics. This Cincinnati-based biotech company is developing AKB-6548, an HIF-PH inhibitor. Akebia was spun off from Procter & Gamble Pharmaceuticals in 2007. AKB-6548 is an orally bioavailable HIF-PH inhibitor that is in Phase II clinical trials for anemia associated with CKD. AKB-6548 is viewed by nephrologists similarly to FG-4592/ASP 1517 in terms of familiarity, interest, and percentage of patients likely to be candidates. At this point, our survey shows that nephrologists differentiate very little between AKB-6548 and FG-4592/ASP 1517.
- Rockwell Medical. Soluble ferric pyrophosphate (SFP), a late-stage investigational drug for iron therapy treatment, delivers iron in a non-invasive, physiologic manner to dialysis patients via dialysate during their regular dialysis treatment. Despite the publication of positive Phase II top-line results, there continues to be low familiarity with SFP, but nephrologists were moderately interested after review of a short product description. The recent trials also showed that SFP allowed for reducing the dose of ESAs (i.e., the SFP arm required 37.1% less ESA dose compared to placebo). 3 And, just over a majority of nephrologists surveyed do highly believe that SFP will enable them to reduce their use of ESAs.1
Bone and mineral metabolism
- Keryx Biopharmaceuticals, Vifor Fresenius Medical Care Renal Pharma. Keryx’s Zerenex and Vifor’s PA21 are two compounds in late-stage development for the treatment of hyperphosphatemia. Both products are iron-based phosphate binders that will compete in a crowded market with the likes of Sanofi’s sevelamer (Renagel / Renvela), calcium acetate, and Shire’s Fosrenol. Keryx announced top-line Phase III trial results in January 2013 and Vifor has announced that the U.S. Food and Drug Administration has accepted their new drug application for PA21 and indicated a Prescription Drug User Fee Act date of Dec. 1. While surveyed nephrologists believe that iron-based binders will have less value to their practice compared to oral HIF-PH inhibitors, interest is still moderate and 20%-25% of patients in CKD-ND and 30%-40% of dialysis patients would be likely candidates for these binders, respectively. It will be interesting to see market changes when and if these new iron-based products launch, especially after generic sevelamer is available in 2014.1
PA21 offers a key benefit of low pill burden compared to sevelamer carbonate, which may help with compliance-related issues.. Zerenex has met key secondary end points in its trials of increasing ferritin and transferrin saturation (TSAT) and reducing the use of IV iron and ESAs versus the active control over the 52-week safety assessment period of the study. Despite these clinical trial results, slightly fewer than 60% of nephrologists surveyed indicated either neutral or low believability in whether Zerenex will enable them to reduce their use of IV iron in dialysis patients.1
More in the pipeline
Other products in development include:
– AMG-416, a peptide agonist of the human cell surface calcium-sensing receptor (CaSR) being investigated as a treatment for secondary hyperparathyroidism from Amgen,
– Patiromer (RLY5016) a non-absorbed oral potassium binder being developed by for the management of elevated serum potassium levels, among other agents. Among the options presented to nephrologists describing products in development, they perceive a non-absorbed oral potassium binder to be statistically equal to that of a HIF-PH inhibitor and a biomarker for acute kidney injury.
It is certain that the renal market—as well as nephrologists’ perceptions of treatments—will continue to change as more trial results become available.
1. BioTrends Research Group Treatment Trends: Nephrology Q12013 (U.S.) publication.
2. Data accessed from www.clinicaltrials.gov and press releases / company websites,including FibroGen website and press releases (12/11/2012, 11/5/2012, 6/4/2012, and 5/3/2011) and Akebia Therapeutics website press release 4/5/2012.
3. At the time of fielding the TreatmentTrends: Nephrology Q1 2013 (U.S.) survey, Rockwell Medical announced the SFP arm required 37.1% less ESA dose compared to placebo on Feb. 4. However, a subsequent announcement on May, 20 included the fully-analyzed data, which supersedes initial top-line data announced, and noted the SFP arm required 35% less prescribed ESA dose compared to placebo.