Rienhoff Syndrome

Just as 2021 was wrapping up, the U.S. Food and Drug Administration (FDA) had some end-of-year activity. Here’s a look. FDA Approved Xeris’s Recorlev for Cushing’s Syndrome On December 30, 2021, the FDA approved Chicago-based Xerix Biopharma Holdings’ Recorlev (levoketoconazole) for endogenous hypercortisolemia in adults with Cushing’s syndrome where surgery is not an option or hasn’t been curative. The approval was built on data from two positive Phase III trials. Both hit their primary endpoints. Endogenous Cushing’s syndrome is a rare and potentially fatal endocrine disease caused by chronic increased cortisol exposure, often resulting from a benign pituitary gland tumor. The tumor causes the body to overproduce high cortisol levels for an extended time. It is most common in adults from 30 to 50 years of age and affects women three times more than men. Recorlev is a cortisol synthesis inhibitor. It is the pure 2S,4R enantiomer of ketoconazole, a steroidogenesis inhibitor. It received Orphan Drug Designation from both the FDA and the European Medicines Agency (EMA) for endogenous Cushing’s syndrome. “We are thrilled with the FDA’s approval of Recorlev as a safe and effective treatment option for patients with endogenous Cushing’s syndrome,” said Paul R. Edick, Chairman and Chief Executive Officer of Xeris. “With this approval, Xeris’ experienced endocrinology-focused commercial organization can begin rapidly working to help address the needs of Cushing’s syndrome patients in the U.S. who are treated with prescription therapy.” Mesoblast Provides Update on FDA Meeting Over CRL for Remestemcel-L In October 2020, the FDA issued a Complete Response Letter (CRL) to Mesoblast for its Biologics License Application (BLA) for Ryoncil (remestemcel-L). The company had applied for approval of the drug for pediatric steroid-refractory acute graft versus host disease (SR-aGVHD). It was surprising because the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9 to 1 to recommend the drug in mid-August. On December 30, 2021, the company offered a regulatory update on the drug after a meeting with the FDA’s Office of Tissues and Advanced Therapies (OTAT). The company suggested ways of addressing the deficiencies in the CRL, including the appropriateness of a potency assay and outstanding chemistry, manufacturing and controls (CMC) issues. The OTAT said the company’s approach to the CMC issues was reasonable and that the in vitro immunomodulatory activity of the drug proposed was also a reasonable critical quality attribute (CQA) for the product. Mesoblast indicated it “has now generated substantial new data which it believes establish the relevance of the proposed in vitro immunomodulatory activity of remestemcel-L to the clinical effect of the product in the completed Phase III trial in pediatric SR-aGVHD, including to survival outcomes and biomarkers of the product in vivo activity. Mesoblast will provide these new data to OTAT and address other remaining CRL items as required for the BLA resubmission.” GVHD is a severe inflammation caused by bone marrow transplant complications. It appears in up to half of the 30,000 people who receive an allogeneic bone marrow transplant annually, mostly in blood cancers. Mortality can be as high as 90% in the most severe form of GVHD. There are no approved therapies for SR-aGVHD in children under 12.