Risedronate Sodium

A new study suggests that adding common bone loss drugs to azoles can improve efficacy when treating fungal infections. Human skin, hair and nails are all vulnerable to fungal infections. While these infections are usually not serious, they're difficult to fully resolve and often recur after treatment -- sometimes for years. They're also often resistant to treatments, including a common class of antifungals called azoles. A study published this week in mSphere points to a new way to boost the efficacy of azoles in treating those infections -- combining them with commonly available drugs called bisphosphonates, usually used to treat osteoporosis. Previous work by the same research group has shown that adding bisphosphonates to azoles can effectively treat yeast infections from Candida and Cryptococcus species. The new study extends that finding to dermatophytes, which cause superficial infections. The study suggests that bisphosphonates could be repurposed to use with azole antifungals, which are relatively nontoxic, and that the combination could be readily tested in clinical studies. "There aren't many good antifungal drugs around, and the fungus will always develop resistance no matter how you treat them," said senior author Dee Carter, a mycologist at the University of New South Wales, Australia. "For what we're proposing, to use 2 drugs at the same time, that resistance is much less likely." Carter says she was only a little surprised to see the synergistic effect in dermatophytes. This research project began years ago, she says, when her group conducted a series of genomic analyses on the response of pathogenic yeasts to drug treatment. That study led them to a genetic pathway that is "upstream" of the pathway targeted by azoles, and is instead targeted by bisphosphonates. "That's often a good way to get drugs to work, is to target processes that are interlinked like that," Carter said. In the lab, Carter and her team tested 3 commonly available bisphosphonates (risedronate, alendronate and zoledronate) in combination with 3 commonly available azole antifungals (fluconazole, itraconazole and ketoconazole). They tested these against clinical isolates from a diverse range of dermatophyte species that cause superficial infections. The combination of zoledronate and ketoconazole proved particularly effective against 8 of the 9 tested species. It also prevented the development of resistance. Aidan Kane, mycologist, lead author of the study and a Ph.D. student in Carter's lab, used fluorescence microscopy and other methods to show that the drug combination worked by weakening the cell membrane enough that the fungus could not survive. Beyond the dermatophytes, the group also found that bisphosphonate-azole combinations could act against molds that cause invasive disease, suggesting another possible clinical application for the drugs. "You can use these combinations directly for superficial infections, like Candida or dermatophyte infections, and we're hoping that with modified forms of the drugs we can create something that will also work systematically," Carter said. "The next step is to continue testing bisphosphonate-azole combinations in animal models, and then test it in clinical trials."

There are several companies facing decisions by the U.S. Food and Drug Administration (FDA) this upcoming week. However, it should be noted that because the upcoming weekend is the Memorial Day holiday in the United States, some of these decisions may be made before their dates to avoid the holiday. Here’s a look. There are several companies facing decisions by the U.S. Food and Drug Administration (FDA) this upcoming week. However, it should be noted that because the upcoming weekend is the Memorial Day holiday in the United States, some of these decisions may be made before their dates to avoid the holiday. Here’s a look. Dova Pharmaceuticals. On Monday, May 21, the FDA is expected to make a decision on Dova Pharmaceuticals ’ New Drug Application (NDA) for avatrombopag for thrombocytopenia in patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. The submission was built on two identically-designed Phase III clinical trials, ADAPT 1 and 2. Avatrombopag met all primary and secondary endpoints with high statistical significance. The application was accepted under a Priority Review status, which moved the review time from 10 months to a goal of six months. The drug is a second generation orally administered TPO-RA. In a November 2017 statement, Alex Sapir, president and chief executive officer of Dova, said, “We are extremely pleased that FDA has accepted our NDA submission with Priority Review. We believe that avatrombopag represents a novel treatment option with robust efficacy as well as an improved safety pro compared to platelet transfusions, today’s current standard of care. We look forward to working closely with FDA through the review process.” BioMarin Pharmaceutical. BioMarin , headquartered in San Rafael, California, is awaiting an FDA decision on its Biologics License Application (BLA) for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product to treat adults with phenylketonuria (PKU) who have problems controlling their blood phenylalanine levels despite previous treatment with available therapeutics, including sapropterin. The PDUFA goal date is Friday, May 25. The drug is also being evaluated by the European Medicines Agency (EMA). In a March 28 statement, Hank Fuchs, president of worldwide research and development for BioMarin, said, “The acceptance of the pegvaliase application for review by the EMA signifies a milestone in our journey to bring this important treatment to patients and families worldwide, offering a new option with the potential to alter the course of lifelong PKU management. For more than 10 years, we have been committed to advancing the development of therapies for the PKU community, and we look forward to working with European regulatory authorities on the pegvaliase application.” Recro Pharma Based in Malvern, Pennsylvania, Recro has a PDUFA date of Saturday, May 26 for its New Drug Application (NDA) for intravenous meloxicam 30mg to manage moderate to severe pain. The IV formulation was designed using the NanoCrystal platform, which allows for enhanced bioavailability of poorly water-soluble drugs. NanoCrystal is a registered trademark of Alkermes Pharma Ireland Limited (APIL). Amgen The FDA has assigned Amgen a PDUFA action date of Monday, May 28, which happens to be Memorial Day in the U.S., for its supplemental BLA (sBLA) for Prolia (denosumab) to treat patients with glucocorticoid-induced osteoporosis (GIOP). The sBLA was submitted on July 28, 2017, and utilized data from a Phase III clinical trial comparing Prolia to risedronate in patients receiving glucocorticoid treatment. Glucocorticoid drugs that are often used to treat inflammatory conditions have numerous side effects, including bone loss. “We believe that Prolia can address a critical treatment need for patients with glucocorticoid-induced osteoporosis, which is the most common drug-induced form of the disease,” said Sean Harper, Amgen’s executive vice president of research and development in an October 2017 statement. “We will continue to work closely with the FDA as they review our application and look forward to expanding Prolia’s benefits to patients with this serious condition that is often underestimated and untreated.”