Expert opinion on investigational drugs
-
Expert Opin Investig Drugs · Jul 2020
ReviewTeprotumumab: a novel therapeutic monoclonal antibody for thyroid-associated ophthalmopathy.
Thyroid-associated ophthalmopathy (TAO) is a disfiguring, potentially blinding, and sub-optimally managed autoimmune condition. Current therapy of active TAO consists most frequently of glucocorticoid steroids, orbital radiation, or B-cell depletion; all of which are associated with substantial side effects. Teprotumumab (Tepezza) is a human monoclonal antibody against the insulin-like growth factor type I receptor (IGF-IR), recently evaluated in two clinical trials for active moderate-to-severe TAO that was recently approved by the United States Food and Drug Administration (FDA) for use in TAO. ⋯ Teprotumumab has demonstrated substantial and rapid improvement in Clinical Activity Score and proptosis reduction in TAO compared to placebo. Subjective diplopia and quality of life were also improved in both clinical trials. Teprotumumab exhibited a favorable safety profile, with transient hyperglycemia, muscle cramps, and auditory side effects being associated with the drug; these were usually transient. The trial findings indicate that teprotumumab is a promising, potential first-line therapy for treating TAO.
-
Expert Opin Investig Drugs · May 2020
ReviewRuxolitinib: a potential treatment for corticosteroid refractory acute graft-versus-host disease.
Allogeneic transplantation represents a potentially curative procedure for various lethal conditions; however, it is associated with serious immune mediated complications. The most serious complication is graft-versus-host disease (GVHD). Acute GVHD (aGVHD) is unresponsive to initial corticosteroid therapy in ~40% of cases. Corticosteroid-refractory aGVHD (CR-aGVHD) represents a significant unmet need with nearly 60% mortality in patients developing this state. ⋯ Ruxolitinib represents the standard option for CR-aGVHD. Future studies should identify patients less likely to respond to ruxolitinib and/or focus on a more targeted approaches to reduce infectious complications and cytopenias seen with this drug.
-
Expert Opin Investig Drugs · Feb 2020
ReviewElafibranor: a potential drug for the treatment of nonalcoholic steatohepatitis (NASH).
Introduction: Nonalcoholic fatty liver disease (NAFLD) encompasses a progressive disease phenotype starting from simple steatosis, which can progress to nonalcoholic steatohepatitis (NASH). It is component of the metabolic syndrome with a large impact on mortality in these patients. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and insulin metabolism, two key components in pathophysiology of NAFLD and NASH. ⋯ Expert opinion: Current data support an effect of elafibranor on the resolution on NASH and the improvement of two key drivers of NASH progression - insulin resistance and serum lipid normalization. The safety profile is favorable, though reversible serum creatinine elevations occur with use, potentially limiting its use in patients with concurrent renal disease. The modest effect sizes in different NAFLD disease stages of elafibranor and other drugs in development for NASH, will likely lead to pursuing of drug combinations personalized to each stage of the NAFLD disease spectrum.
-
Expert Opin Investig Drugs · Jan 2020
ReviewPersonalized pharmacological therapy for ARDS: a light at the end of the tunnel.
Introduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes. ⋯ Personalized medicine targeting the different ARDS phenotypes has emerged as an option to improve survival. Identification of specific ARDS patient phenotypes that respond to specific therapies seems to be the most important challenge for the next decade. Additional research is warranted before personalized medicine approaches can be applied at bedside for ARDS patients.
-
Expert Opin Investig Drugs · Dec 2019
ReviewBIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.
Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093. ⋯ For the GAMES trials, we review data on objective biological variables, adjudicated edema-related endpoints, functional outcomes, and mortality which, despite missing the primary endpoint, supported the initiation of a Phase 3 trial in LHI (CHARM). For the TBI trial, we review data on MRI measures of edema and the initiation of a Phase 2 trial in contusion-TBI (ASTRAL). Expert opinion: Emerging clinical data show that BIIB093 has the potential to transform our management of patients with LHI, contusion-TBI and other conditions in which swelling leads to neurological deterioration and death.