Epoetin alfa(Sandoz International GmbH)

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. 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.

The U.S. Food and Drug Administration (FDA) and some biosimilar and generic drug advocates were concerned that the naming for biosimilars—the branded drug’s name and a unique, four-letter suffix—made the drugs sound inferior to consumers than their branded counterparts. The U.S. Food and Drug Administration (FDA) and some biosimilar and generic drug advocates were concerned that the naming for biosimilars—the branded drug’s name and a unique, four-letter suffix—made the drugs sound inferior to consumers than their branded counterparts. So in January 2017, the agency decided to retroactively add a suffix to all previously approved biologic drugs. Now they’ve changed their mind . And it seems likely consumers won’t notice one way or the other. A biologic drug, or biologics, is produced from living organisms. Most of the current top-selling drugs in the world, like AbbVie’s Humira, are biologics. But some classic older drugs, like insulin, are also biologics. A biosimilar is, essentially, a generic version of a biologic. However, unlike a generic of a small-molecule drug, which is an exact copycat, biosimilars are—as the word implies—similar to the brand drug, but not an exact copycat. As such, they are required to go through an approval process similar to that of the original branded medicines. Their clinical activity is identical or extremely close, but there is concerns that the labeling implies the biosimilars aren’t as effective or as safe as the originator drugs. Given that most of the new biologics are extremely expensive, the federal government has targeted biosimilars, which are slightly less expensive than their branded brethren, as a potential solution to the problem of high drug prices. The biosimilar market in the U.S. has been slow to catch on, especially compared to Europe. In mid-2018, the FDA launched its Biosimilars Action Plan which, according to Commissioner Scott Gottlieb, was designed to help “make the process for developing biosimilars more efficient.” At that time, there were only three biosimilars on the market in the U.S., although 11 had been approved. Many companies slowed market penetration via lawsuits and pay-to-delay schemes, which the FDA is also targeting. In a statement yesterday, Gottlieb noted, “By applying this policy to originator and biosimilar products alike, the FDA sought to advance the goal of patient safety—which the suffixes promote—without creating a misimpression that products with such suffixes are somehow inferior to those without. In addition, the FDA announced in that guidance that the agency was considering the process to retrospectively change the names of biological products already on the market, to begin adding distinguishable suffixes.” Although the change is likely to appease some in the industry, it seems unlikely that the average consumer will note the difference or even be familiar with the terms “biologics” or “biosimilars.” They are much more likely to be told by their pharmacist or physician that they are receiving a generic version of whatever drug they are expecting. Biosimilars Review & Report , clearly not a typical consumer, notes , “The continuing use of the 4-letter suffix is controversial not only because of the reasons stated by Dr. Gottlieb, but also because these designations have not been used to any significant extent in safety reporting. As stated here and in Biosimilar Development , these suffixes have been reported in fewer than 5 percent of all drug safety reports filed with the FDA to date (but without causing issues as to which biosimilar was associated with an individual report). The updated guidance reaffirms the FDA’s commitment to the use of these suffixes.” The Biosimilars R&R article points out that the FDA policy isn’t likely to make a difference in terms of pharmacovigilance security, partly because, even for people in the field, the suffixes are difficult to remember, which is “precisely why they will not generally be used in drug adverse event reporting.” So far, 17 biosimilars approved by the FDA have been approved with a suffix, and the 27 originator biologics have hit the market with the four-letter additions. Gottlieb stated, “We expect that as time goes on, and more biological products are introduced to the market with distinguishable suffixes, patients and providers increasingly will understand that the suffixes reflect a consistent naming convention and are not an indicator of product quality.” Will this solve what the FDA views as a problem? Well, the naming convention was confusing before and this doesn’t seem to do anything more than confuse it more. Part of the problem is simply that drugs can have too many names, regardless of whether they are small-molecule drugs or biologics. The FDA document on the changes has a glossary that defines “core name,” “nonproprietary name,” “proper name,” “proprietary name” and several other terms such as “biosimilar product,” “interchangeable product,” and “originator biological product.” One example is Amgen’s Neupogen (the proprietary name or brand name), which has a core name of “filgrastim” and “epoetin alfa.” Pfizer’s biosimilar of Neupogen has a brand name of Nivestym, whose core name is filgrastim-aafi. Novartis’s Sandoz biosimilar for Neupogen has a proprietary/brand name of Zarxio, with the core name filgrastim-sndz. For all that, while the FDA believes this will provide clarity and help biosimilars enter the market, many in the industry believe the opposite. C hristine Simmon, executive director of the Biosimilars Council, a division of the Association for Accessible Medicines (AAM), stated , “FDA’s current requirement of suffixes presents a significant, artificial barrier to biosimilars that is misaligned with the agency’s own Biosimilars Action Plan and the Trump administration’s commitment to lowering drug prices for America’s patients.”