linezolid associated triad of acute pancreatitis lactic acidosis and hypoglycemia a rare case report and literature review

Original title: “Linezolid-Associated Triad of Acute Pancreatitis, Lactic Acidosis, and Hypoglycemia: A Rare Case Report and Literature Review.”

False negative results from RCTs ... ultra-rare diseases. Rezolute’s experience developing a therapy in this setting serves as a case study illustrating both these limitations and potential approaches to overcoming them. Rezolute is studying its first-in-class monoclonal antibody therapy, ersodetug (“erso”), in two Phase 3 trials for the treatment of hypoglycemia ... False negative results from RCTs underscore the inadequacy of this “gold standard” for demonstrating therapeutic benefit in patients suffering from certain ultra-rare diseases. Rezolute’s experience developing a therapy in this setting serves as a case study illustrating both these limitations and potential approaches to overcoming them. Rezolute is studying its first-in-class monoclonal antibody therapy, ersodetug (“erso”), in two Phase 3 trials for the treatment of hypoglycemia resulting from separate but related forms of hyperinsulinism (HI). Our experience in tumor HI shows FDA is willing to set aside the RCT “gold standard” when other clinical evidence supports an alternative path. This demonstrates the agency’s emerging commitment to streamline the regulatory pathway for ultra-rare disease therapies. We hope FDA will continue to work with us and other industry partners in realizing the goal we all share: providing novel, safe, and effective treatments to individuals suffering from severe and debilitating ultra-rare diseases. A tale of different paths for different indications of the same disease It is well known within the biopharma industry that clinical studies can produce It is well known within the biopharma industry that clinical studies can produce any number of unexpected and possibly disappointing outcomes, including false negative results, or in statistical parlance, “Type II errors.” This is particularly true for clinical studies of therapies for ultra-rare diseases, where mechanistic plausibility may have already been demonstrated in open-label studies and expanded access programs (EAPs), but nonetheless must be replicated in randomized, double-blind, placebo-controlled studies (RCTs) that have narrow endpoints and small sample sizes.

Original title: “The conundrum of false negative clinical studies in ultra-rare diseases | STAT”