Clinical trials are a linchpin of clinical science. They are designed to evaluate the prowess of an antibacterial, antifungal, and antiviral compounds. The busy clinical trial terrain results in a barrage of data. Sifting through all this information to discover studies that describe drugs that are practice-changing can be challenging for a busy clinician.
A session at the year’s ID Week in San Diego, California came to the rescue. The speakers were tasked with summarizing recent important clinical trials involving viruses, bacteria, and fungi. Francisco Marty, MD, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, reviewed recent antiviral trials, excepting those involving HIV. His focus was the herpes zoster subunit vaccine, intravenous (IV) influenza drugs, and letermovir
for prevention of post-transplant cytomegalovirus (CMV) infection.
An adjuvanted herpes zoster vaccine that targets the viral glycoprotein E subunit was evaluated in 2 large (over 17,700 subjects total) ZOE-50 and ZOE-70 randomized, placebo-controlled trials (RCTs). The glycoprotein is necessary for viral replication and cell-to-cell spread, and so is a good target. Vaccine efficacy and safety was demonstrated. The prowess of the same vaccine following autologous hematopoietic cell transplantation was evaluated in a phase 1/2 trial of 121 patients. Efficacy and safety were also evident.
Two other trials evaluated IV zanamivir versus oral oseltamivir
for the treatment of severe influenza. These trials have been sorely needed. Approved antivirals for influenza have been limited to mild disease or the outpatient setting. There is a pressing need for an IV option for severe disease. In an open-label phase 2 trial, zanamivir demonstrated tolerable efficacy and safety, and has been used for thousands of emergency responses to influenza. All these reasons have made zanamivir an attractive potential option for oseltamivir-resistant influenza.
Both trials were positive. However, frustratingly, because these are pioneering trials, there is no basis for comparison with other data, which has become a roadblock to those at the US Food and Drug Administration who wield the power of drug approval.
The final antiviral RCT assessed the use of letermovir in preventing CMV infections in high-risk allogeneic hematopoietic stem cell transplant recipients. Letermovir blocks the activity of a viral complex that is essential for replication. Positive phase 2 results spurred a phase 3 RCT featuring a 14-week treatment with letermovir (n=373) or placebo (n=192) and follow-up to 48 weeks. The drug significantly reduced the incidence of CMV infections with comparable safety to the placebo. Approval of the drug is expected in the coming months.
Shifting gears, recent trials in antibacterials were discussed by Susan Rehm, Cleveland Clinic, Cleveland, Ohio. Her task was formidable, given the huge number of trials in the past several years. The trials presented were by no means exhaustive. Investigational antibiotics and abstracts presented at ID Week 2017 were not presented.