January/February 2017: News Briefs

Rapid Withdrawal of Steroids Reduces Incidence of Diabetes Post-Transplant

Initiation of rapid withdrawal from steroids can reduce the incidence of diabetes after a kidney transplant in immunologically low-risk patients, according to research presented during Kidney Week 2016 by Christian Hugo, MD and colleagues. The research was cited in an article in Medpage Today.

The researchers conducted a study among 587 kidney transplant patients who were randomized to one of three arms. Patients in arm A received basiliximab induction with low-dose tacrolimus, 2 g mycophenolate mofetil, and steroid maintenance therapy; arm B received basiliximab induction with low-dose tacrolimus, 2 g mycophenolate mofetil, and rapid steroid withdrawal on day 8; and arm c received antithymocyte globulin (ATG rabbit) induction with low-dose tacrolimus, 2 g mycophenolate mofetil, and rapid steroid withdrawal on day 8.

The incidence of acute rejections at one year post-transplant was the primary end point; the secondary end point was improved safety. There was no significant difference in the incidence of kidney rejection among the three groups, nor were there significant differences in the secondary end points of patient survival at 1 year, death-censored allograft survival at I year, and graft loss or death at 1 year.

However, the incidence of post-transplant diabetes was nearly bisected following rapid steroid withdrawal in arms B and C compared with arm A.

Boxed Warning Removed from Veltassa® Label

In a recent press release, Relypsa, Inc. announced that the FDA has approved a supplemental New Drug Application (sNDA) with key updates to the label of Veltassa® (patiromer) for oral suspension. Veltassa is approved for the treatment of hyperkalemia. The agency has approved the sNDA removing the Boxed Warning from Veltassa®s label. The Boxed Warning recommended taking Veltassa at least 6 hours prior to or after other oral medication. However, based on positive data reported earlier in 2016, the updated label recommends taking Veltassa 3 hours before or after other oral medications.

“We are extremely pleased the FDA has approved these changes to Veltassa’s label, including removal of the Boxed Warning. These important updates are based on our positive data, which showed there is a low risk for drug-drug interactions with Veltassa when it is separated from other oral medications by at least 3 hours,” John A. Orwin, president and chief executive officer of Relypsa, said. “We believe the 3-hour dose separation and addition of data from our drug-drug interaction program to the label can provide doctors greater flexibility in choosing Veltassa and adding it to patients’ daily treatment regimen.”

Results of two studies reported during Kidney Week 2016 found that certain medications taken to treat heartburn, acid reflux, and ulcers may have damaging effects on the kidneys. The medications include proton pump inhibitors (PPIs) and histamine receptor-2 (H2) blockers.

Rigel Announces Phase 2 Results of Drug for IgAN

Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals, Inc., presented a review of products in development at the 35th Annual J. P. Morgan Healthcare Conference in January. One of the products highlighted was fostamatinib for the treatment of IgA nephrology (IgAN), an autoimmune disease of the kidneys.

According to a press release from Rigel, the first cohort in the phase 2 study of fostamatinib in IgAN has been completed in Asia, the United States, and Europe. The cohort aimed to assess the efficacy, safety, and tolerability of fostamatinib at 100 mg twice a day, measured by change in proteinuria, renal function, and histology. At 24 weeks, fostamatinib was well tolerated and had a good safety profile. Initial data suggest a trend toward greater reduction in proteinuria in the fostamatinib group compared with those in the placebo group. Further analysis of the cohort one data, with a focus on the histology review of the renal biopsies (pre- and post-study), is underway; results will be presented later in 2017. A second cohort to evaluate a higher dose of fostamatinib (150 mg) for IgAN will complete enrollment in 2018; full results of cohort two will be presented in 2018.

PPIs and H2 Blockers May Be Associated with Renal Damage

According to an article in Medical News Today, researchers in Italy examined data on 187,330 participants of the Health Professional Follow-Up Study and Nurses’ Health Study I and II to determine if use of PPIs and H2 blockers increased the risk of developing kidney stones. Following adjustment for demographic and clinical factors, there was an association between PPI use and a 12% higher risk of developing a kidney stone; use of H2 blockers was associated with a 13% higher risk.

Pietro Manual Ferraro, MD, MS, PhD, lead author of the report, said, “Use of PPIs and H2 blockers is associated with a small increase in risk of incident kidney stones. Further studies are needed to confirm our findings and to investigate whether the excess risk if related to a particular type of kidney stones such as those made of calcium oxalate.”

In the second study reported at the meeting, researchers led by Yan Xie, MPH, analyzed data from the US Department of Veterans Affairs national database on 153,157 users of PPIs or H2 blockers, there was an association between PPI use and a >30% higher risk of developing chronic kidney disease or a combined endpoint of kidney failure or >50% decline in estimated glomerular filtration rate compared with use of an H2 blocker in the absence of acute kidney injury.

“Reliance on AKI as a marker of potential adverse renal events in those treated with PPI is not sufficient,” Mr. Xie said. “Exercising vigilance in PPI use—even in the absence of AKI—and careful attention to kidney function in PPI users may be a reasonable approach.”

Phase 2 Positive Data on Sparsentan Reported

In a press release from Retrophin, Inc., the company announced additional positive data on results from the phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis (FSGS). FSGS is a rare kidney disorder that does not have any FDA-approved pharmacologic treatment. Results were reported during Kidney Week 2016.

Howard Trachtman, MD, NYU School of Medicine, said, “The prevalence of FSGS is on the rise and without an approved therapy, many patients diagnosed with the disorder face a progressive decline and the high likelihood of end-stage renal disease. These findings from the DUET study underscore the potential of sparsentan as a first-in-class treatment for FSGS.”

Top-line data from those in the sparsentan treatment group achieved statistical significance in reduction of proteinuria, the primary efficacy end point. Following an 8-week, double-blind treatment period, patients treated with sparsentan had a more than two-fold reduction in proteinuria compared with those in the irbesartan group.

In an analysis of the secondary end point data, 28.1% of patients in the sparsentan group achieved modified partial remission of proteinuria, compared with 94% of those in the irbesartan group. In the post hoc, intention-to treat analysis, the sparsentan group demonstrated a more than two-fold reduction of proteinuria, compared with irbesartan. Safety data showed sparsentan was generally safe and well tolerated.

Fresenius Collaborates with The Johns Hopkins Hospitals in Baltimore

Fresenius Kidney Care has announced a collaboration with The Johns Hopkins Hospital to expand critical kidney care services for residents of the Baltimore, Maryland, area. In a press release, Fresenius outlined the eight new care centers in Baltimore, Dundalk, and Lutherville-Timonium, including the only center in Maryland dedicated to treating children with chronic kidney disease.

Bill Valle, executive vice president of Fresenius Medical Care North American and president of Fresenius Kidney Care, said, “Our vision behind these centers aligns with the values we share with The Johns Hopkins Hospital to improve quality of life of every patient, every day. We are excited to join forces with one of the leading and preeminent institutions in the United States in our effort to empower patients throughout their individual journeys so they can continue living life, doing what is important to them and thriving.”

Physicians from The Johns Hopkins Hospital will oversee the management of the centers’ medical operations. Paul Scheel, MD, division chief of the nephrology department at the hospital and vice president of The Johns Hopkins Physicians, will work with medical directors at the new hemodialysis facilities.

“Chronic kidney disease is a considerable, but unrecognized health issue in this country,” Dr. Scheel said. “We are pleased to be a part of this initiative, dedicated to providing optimal dialysis services to our patients.”