Expert opinion on investigational drugs
-
Expert Opin Investig Drugs · Apr 2021
ReviewTargeting FGFR in intrahepatic cholangiocarcinoma [iCCA]: leading the way for precision medicine in biliary tract cancer [BTC]?
Introduction: The increasing availability of next-generation DNA sequencing (NGS) opens the opportunity to tailor therapies to potential targets. Intrahepatic cholangiocarcinoma (iCCA) has the most actionable genomic targets of the hepatobiliary malignancies, including mutations in Isocitrate Dehydrogenase (IDH) and Fibroblast Growth Factor Receptor (FGFR), particularly FGFR2. With the recent accelerated approval of pemigatinib and several trials currently underway, FGFR2 inhibition will set the mold for tailored therapies in hepatobiliary cancer. ⋯ Expert opinion: While more mature data are needed from the trials in progress, currently published analyses show survival benefit with FGFR2 inhibitors in patients positive for FGFR2 fusion who have failed the standard of care. Infigratinib, futibatinib, pemigatinib and derazantinib have all demonstrated promising activity iCCA patients harboring FGFR2 fusion. Eventually, head-to-head trials will be needed to fully understand the benefits of each agent and the role of reversible versus irreversible FGFR2 inhibitors.
-
Expert Opin Investig Drugs · Apr 2021
ReviewDurvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer.
Introduction: The prognosis of patients with advanced biliary tract cancer (BTC) remains dismal, with a 5-year overall survival rate of less than 10%. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of several hematological and solid tumors, controversial results have been reported in BTC. In this setting, the anti-PD-L1 inhibitor durvalumab is currently under investigation in several clinical trials as monotherapy, or in combination with other pharmacological agents. ⋯ Expert opinion: The promising antitumor activity shown by durvalumab in early trials warrants further investigation because it may provide more effective, much needed treatment options. The results of clinical trials of this PD-L1 inhibitor, as a monotherapy or in combination, are eagerly awaited. Future efforts should focus on the identification and development of reliable biomarkers of response to durvalumab in BTC, clarifying the role of PD-L1 expression, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB) and other emerging predictors.
-
Expert Opin Investig Drugs · Dec 2020
ReviewOverview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease.
A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden globally. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. Clinicians are using IL-6 inhibitors to CRS, and researchers are investigating the use of IL-6 inhibitors, namely tocilizumab, sarilumab, siltuximab, in COVID-19 management. ⋯ There is a role for suppressing the immune response with IL-6 inhibitors that will continue to require investigation. These agents are available and have demonstrated a mild safety profile. There may be advantages to a targeted approach to suppressing the hyperinflammatory state of the disease. Timing, the long-term effects, and what cocktail of medications demonstrates the strongest outcomes are all important considerations as IL-6 inhibitors continue to be evaluated in this global pandemic.
-
Expert Opin Investig Drugs · Nov 2020
ReviewMavacamten: a novel small molecule modulator of β-cardiac myosin for treatment of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a common known monogenetic cardiovascular disorder which frequently leads to symptoms such as dyspnea and exercise intolerance. Current guideline-recommended pharmacotherapies have variable therapeutic responses. Mavacamten, a small molecule modulator of β-cardiac myosin, reduces hypercontractility, a central mechanism in the pathogenesis of HCM. Mavacamten has recently been evaluated in Phase 2 and 3 clinic trials for obstructive and nonobstructive symptomatic HCM. ⋯ Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), Overall Summary Score (OSS), and numerical rating scale (NRS) dyspnea scores; and patients with both obstructive and nonobstructive HCM had significant improvement in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.
-
In clinical trial for the Ebola virus, the broad-spectrum anti-viral agent remdesivir was shown to have a good safety profile. Remdesivir is now being tested in severe COVID-19. ⋯ It seems to me that we have learnt very little from the SIMPLE trial, and this would be predicted from a trial that has no control or placebo group. The results of ACTT1 were reported early after an interim analysis showed that a higher than expected number of recoveries had occurred. There was an indication that remdesivir may be reducing mortality, but this was no statistical significance. The trial is continuing, and the final data are eagerly awaited to determine whether remdesivir is a game-changing remedy or a ripple in the ongoing search for a medicine for the treatment of COVID-19.