Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients.

BACKGROUND/OBJECTIVE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD. METHODS: Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment. RESULTS: The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients. CONCLUSIONS: These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.

Active Surveillance for Influenza Reduces but Does Not Eliminate Hospital Exposure to Patients With Influenza.

OBJECTIVE To describe the frequency, characteristics, and exposure associated with influenza in hospitalized patients in a Toronto hospital DESIGN/METHOD Prospective data collected for consenting patients with laboratory-confirmed influenza and a retrospective review of infection control charts for roommates of cases over 3 influenza seasons RESULTS Of the 661 patients with influenza (age range: 1 week-103 years), 557 were placed on additional precautions upon admission. Of 104 with symptoms detected after admission, 57 cases were community onset and 47 were nosocomial (10 nosocomial were part of outbreaks). A total of 78 cases were detected after admission exposing 143 roommates. Among roommates tested for influenza after exposure, no roommates of community-onset cases and 2 of 16 roommates of nosocomial cases were diagnosed with influenza. Of 637 influenza-infected patients, 25% and 57% met influenza-like illness definitions from the Public Health Agency of Canada (PHAC) and Centers for Disease Control and Prevention (CDC), respectively, and 70.3% met the Provincial Infectious Diseases Advisory Committee (PIDAC) febrile respiratory illness definition. Among the 56 patients with community-onset influenza detected after admission, only 13%, 23%, and 34%, met PHAC, CDC, and PIDAC classifications, respectively. CONCLUSIONS In a setting with extensive screening and testing for influenza, 1 in 6 patients with influenza was not diagnosed until patients and healthcare workers had been exposed for >24 hours. Only 30% of patients with community-onset influenza detected after admission met the Ontario definition intended to identify cases, hampering efforts to prevent patient and healthcare worker exposures and reinforcing the need for prevention through vaccination. Infect Control Hosp Epidemiol 2017;38:387-392.