National Kidney Month: A Look at Biopharma's Progress in Kidney Diseases
March is National Kidney Month, with March 14 designated as World Kidney Day. The kidneys are called the body’s chemical factories. Their job is to filter waste and perform specific important jobs like controlling red blood cell production and blood pressure.
There are a broad range of diseases of the kidney, ranging from chronic kidney disease (CKD) to types of renal cancer. In the U.S., 26 million people over the age of 20 have CKD. Diabetes is the leading cause of kidney failure in the U.S., with high blood pressure the second leading causes.
With that as a backdrop, let’s look at some recent kidney-related biopharma news.
AstraZeneca’s Roxadustat for Anemia in CKD
On December 18, 2018, AstraZeneca released data from the Phase III OLYMPUS and ROCKIES trials of roxadustat in patients with anemia in chronic kidney disease (CKD) that are either not dependent on dialysis or are dependent on dialysis, respectively. The drug is being jointly developed and commercialized by AstraZeneca and FibroGen.
The OLYMPUS trial compared roxadustat to placebo for patients with anemia in CKD stages 3, 4 and 5 whose disease progression was moderate to severe and who are non-dialysis dependent. That trial met its primary efficacy endpoint, demonstrating statistically significant and clinically meaningful improvement in hemoglobin levels averaged over weeks 28 to 52 compared to placebo. That trial looked at 2,781 patients in 26 countries.
The ROCKIES trial evaluated roxadustat versus epoetin alfa in dialysis-dependent anemia in CKD patients. It too met its primary efficacy endpoint, demonstrating statistically significant improvement in mean change from baseline in Hb levels averaged over weeks 28 to 52. ROCKIES involved 2,133 patients in 18 countries.
“These results add to the growing body of evidence for roxadustat, which is part of the largest clinical program worldwide in evaluating the novel class of HIF-PHI,” stated Sean Bohen, AstraZeneca’s executive vice president, Global Medicines Development and chief medical officer. “This is a significant milestone in the role roxadustat can play to help address a high unmet need in anemia associated with chronic kidney disease, which today is under diagnosed and in many cases under treated.”
Alexion’s Ultomiris for Ultra-Rare Kidney Disease
In late January, Boston-based Alexion’s Ultomiris (ravulizumab-cwvz) hit its primary objective in its Phase III study of complement inhibitor-naïve patients with atypical hemolytic uremic syndrome (aHUS).
aHUS is a chronic, progressive and debilitating ultra-rare disease. It affects children and adults and can lead to irreversible kidney damage as well as affecting other vital organs. It can result in sudden and progressive kidney failure and premature death. The disease symptoms include inflammation and the formation of blood clots in small blood vessels throughout the body mediated by uncontrolled activation of part of the immune system called the complement system.
In the trial, 53.6 percent of patients receiving Ultomiris showed complete thrombotic microangiopathy response, giving immediate and complete inhibition of the complement C5 protein. This was sustained over the eight-week dosing interval.
The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function. Those receiving the drug had reduced thrombocytopenia, reduced destruction of red blood cells, and improved kidney function.
Merck’s Keytruda With Inlyta in Renal Cell Carcinoma
At the American Society of Clinical Oncology 2019 Genitourinary Cancers Symposium (ASCO GU) held in mid-February, Merck & Company presented survival data from its pivotal Phase III KEYNOTE-426 clinical trial of its checkpoint inhibitor Keytruda in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for the first-line treatment of advanced or metastatic renal cell carcinoma (RCC). The company had announced in October 2018 that the trial met both primary endpoints of overall survival (OS) and progression-free survival (PFS), as well as the key secondary endpoint of objective response rate (ORR).
The company released its first interim analysis, showing that Keytruda with axitinib, compared to Pfizer’s Sutent (sunitinib), significantly improved OS, reduced the risk of death by almost half, as well as PFS and ORR. “Merck is pursuing a broad clinical program in advanced cancers of the kidney, prostate and bladder with the goal of advancing new treatment options for patients afflicted by historically difficult to treat malignancies,” stated Roger M. Perlmutter, President, Merck Research Laboratories.
Bristol-Myers Squibb’s Opdivo Plus Yevoy in RCC
At the same meeting, Bristol-Myers Squibb Company presented new data from its Phase III CheckMate-214 study. This is a Phase III, randomized, open-label trial evaluating the combination of Opdivo plus Yervoy versus sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). With a minimum follow-up of 30 months, patients who were intermediate and poor-risk were randomized to receive Opdivo plus low-dose Yervoy. This group continued showing a significant overall survival (OS) benefit compared to those who just received sunitinib. Also, at 30 months, the ORR per investigator for intermediate- and poor-risk patients with the Opdivo-Yervoy combination improved compared to the previous 17.5-month analysis.
“The results from this 30-month follow-up from the CheckMate-214 study are meaningful as they continue to demonstrate that in patients with advanced renal cell carcinoma, a population with considerable unmet treatment needs, there is potential for long-term survival benefits with the combination of nivolumab and ipilimumab,” stated Nizar M. Tanniri, study investigator and physician at The University of Texas MD Anderson Cancer Center.
Xynomic Pharma and Bison Capital Acquisition Given Go-Ahead in China, Spain and Poland for Phase III RCC Trials
On March 16, Xynomic Pharma, a U.S.-China oncology drug development company and Bison Capital Acquisition, jointly announced that China, Spain and Poland's regulators had approved the company’s application to conduct Phase III trials using Xynomic’s abexinostat in combination with Novartis’ Votrient (pazopanib) in patients with RCC. The trials are expected to launch in those countries and additional European countries in the first half of this year. The same trial is currently ongoing in the U.S. and South Korea.
On Feb. 23, Xynomic Pharmaceuticals announced it had dosed the first patient in South Korea in the abexinostat/pazopanib trial as a first- or second-line therapy against RCC.
Abexinostat is a novel, pan-HDAC inhibitor developed by Pharmacyclics and licensed to Xynomic. It is also in trials for B-cell lymphoma.