Author Interviews, Hospital Acquired, Infections, Merck / 16.04.2019

MedicalResearch.com Interview with: Elizabeth Rhee, MD Executive Director, Infectious Disease Clinical Research Merck Research Laboratories MedicalResearch.com: What is the background for this study? Would you briefly explain the condition of ventilated nosocomial pneumonias? Dr. Rhee: Nosocomial pneumonia (NP) is a lung infection that occurs during a hospital stay. NP is often serious, and is associated with high mortality. It is one of the most common health-care associated infections in both the U.S. and Europe, accounting for over 20% of such cases. Gram-negative bacteria, mainly Pseudomonas aeruginosa (PSA) and Enterobacteriaceae, are frequent causes of nosocomial pneumonia. Limited options currently exist for the management of NP caused by Gram-negative pathogens. This is concerning because rates of resistance to Gram-negative bacteria are growing, and they are becoming increasingly difficult to treat. Forms of nosocomial pneumonia include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and ventilated HAP. High rates of death (ranging from 20% to more than 50%) are especially associated with ventilated HAP. Pseudomonas aeruginosa, a Gram-negative bacterium, is the most common cause of HAP/VAP in both the U.S. and Europe. Patients with NP are often critically ill, requiring ventilator support and time in intensive care, and it was important to look at this population as we explore new options for the treatment of NP. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including multi-drug resistant (MDR) P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g ceftolozane/0.5g tazobactam) q8h. C/T is currently being studied at an investigational new dose of 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial. (more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 10.04.2019

MedicalResearch.com Interview with: Michael F. Egan, MDVice President,  NeuroscienceGlobal Clinical DevelopmentMerck Research LaboratoriesNorth Wales, PAMichael F. Egan, MD Vice President,  Neuroscience Global Clinical Development Merck Research Laboratories North Wales, PA  MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration. Amyloid is made up of  a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP.  In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta.  A previous trial in subjects with dementia due to AD failed to find evidence of efficacy. One possible reason for this failure is that subjects had too much amyloid in their brain already. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Hospital Acquired, Infections, Kidney Disease, Merck / 06.10.2018

MedicalResearch.com Interview with: Michelle Hoffman Brown Associate Principal Scientist Merck MedicalResearch.com: What is the background for this study? What are the kidney risks of using colistin to treat carbapenem-resistant bacterial infections? Response: Gram-negative pathogens are responsible for half of all healthcare-associated infections and their ability to resist traditional antibiotics makes them more dangerous for seriously ill patients in a healthcare setting. The need for new approaches to treat these pathogens is essential and this trial aimed to evaluate the efficacy and safety of imipenem/relebactam (IMI/REL) for the treatment of these challenging infections. Nephrotoxicity is a common complication of colistin-based therapy and is the potential adverse experience of greatest concern to prescribing clinicians, limiting its use to treat carbapenem-resistant bacterial infections. Relebactam is a novel β-lactamase inhibitor that restores imipenem activity against many imipenem-non-susceptible strains of Gram-negative pathogens. In the Phase 3 RESTORE-IMI 1 study (NCT02452047), IMI/REL was shown to be as effective as, but better tolerated than, colistin plus imipenem, including as demonstrated by a lower incidence of treatment-emergent nephrotoxicity (prespecified secondary endpoint). This analysis looked at additional renal safety data from the RESTORE-IMI 1 trial.  (more…)
Author Interviews, HIV, Merck / 02.08.2018

MedicalResearch.com Interview with: merck Kathleen Squires MD Director, Division of Infectious Diseases Jefferson University Hospitals and Ming-Tai Lai, PhD Senior Principal Scientist, Biology Discover Merck   MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Squires: The DRIVE-FORWARD study is a pivotal, randomized, double-blind, Phase 3 study that evaluated the safety and efficacy of doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor (NNRTI) in treatment-naïve adults with HIV-1 infection. Data from week 48 of this trial have previously been presented demonstrating that doravirine met its primary endpoint of non-inferior efficacy compared to ritonavir-boosted darunavir (DRV+r). In addition, at 48 weeks, a secondary endpoint showed that the doravirine-treated group had statistically significant lower levels of fasting LDL-C and non-HDL-C versus the DRV+r group. The data presented at AIDS 2018 are week 96 data from the DRIVE-FORWARD trial. At week 96, the doravirine group demonstrated efficacy of 73.1% compared with 66.0% in the DRV+r group, a treatment difference of 7.1% (95% CI: 0.5, 13.7)  Two participants in the DOR treatment group developed genotypic and phenotypic resistance to DOR through 96 weeks of treatment. The rate of discontinuation of therapy due to adverse events was 1.6 percent in the DOR group and 3.4 percent in the DRV+r group. Doravirine is a late-stage investigational NNRTI for the treatment of HIV-1 infection in treatment-naïve adults and is being evaluated both as a once-daily single-entity tablet in combination with other antiretroviral agents, and as a once-daily fixed-dose combination regimen with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF). Earlier this year, Merck announced that the FDA accepted for review two New Drug Applications (NDAs) for doravirine for the treatment of HIV-1 infection in treatment-naïve adults. The NDAs are based upon the findings at week 48 of two ongoing Phase 3 trials, DRIVE-FORWARD and DRIVE-AHEAD, evaluating the efficacy and safety of doravirine and the fixed-dose combination regimen of DOR/3TC/TDF, respectively. The FDA has set a target action date of October 23, 2018 for both applications. Dr. Lai: This study aimed to characterize the mutant viruses selected in treatment-naïve participants through week 48 from DRIVE-FORWARD and DRIVE-AHEAD, and to assess the impact of selected mutations on non-nucleoside reverse transcriptase inhibitor (NNRTI) susceptibility and viral fitness. All of the seven doravirine (DOR)-resistant mutants are either partially susceptible or susceptible to etravirine. Mutants containing the F227C substitution were shown to be hypersusceptible to some nucleoside reverse transcriptase inhibitors (NRTIs) such as azidothymidine (AZT), tenofovir (TFV), lamivudine (3TC), and MK-8591. Among the 12 participants who developed efavirenz (EFV) resistance, 9 of the EFV-resistant clinical mutants were susceptible to DOR with fold-change <2.5. The majority of DOR-selected viruses identified in the treatment-naïve participants in clinical trials to date retain susceptibility to etravirine and hypersensitivity to some NRTIs, with low replication capacity. In addition, the majority of EFV-selected viruses retain susceptibility to DOR.  (more…)
ASCO, Author Interviews, Dermatology, Melanoma, Merck, University of Pittsburgh / 05.06.2018

MedicalResearch.com Interview with: Dr. Diwakar Davar, MD Assistant Professor of Medicine Division of Hematology/Oncology University of Pittsburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The optimal surveillance strategy to detect recurrence in cutaneous melanoma remains elusive. Risk of recurrence increases with higher stage, and is especially high for patients with stage IIIC disease. Although consensus guidelines agree on surveillance imaging for high-risk (stage IIB-IIIC) MEL, there is no consensus regarding optimal frequency/modality in these patients. NCCN guidelines suggest chest radiography (CXR) at 6- to 12-month intervals for stage IA-IIA melanoma  patients; although this is controversial. There exists a great deal of practice variation in the surveillance of these patients. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: High-risk patients, such as the critically ill, with suspected bacterial infections require prompt treatment with appropriate empiric therapy to improve survival. Given the high prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa in the ICU setting, new safe and broadly effective treatment options are needed for critically ill patients requiring antipseudomonal agents. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including MDR P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g/0.5g) q8h. C/T is currently being studied at 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial. This Phase 1 pharmacokinetic (PK) study investigated the penetration of a 3g dose of C/T in the epithelial lining fluid (ELF) of ventilated patients with proven or suspected pneumonia. This is the dose and patient population being evaluated in ASPECT-NP. ELF lines the alveoli, and investigators took samples in a group of 26 patients to see what amount of C/T was in the lung and what was circulating in the plasma during the dosing intervals. In mechanically ventilated critically ill patients, the 3g dose of C/T achieved ≥50% lung penetration (relative to free plasma) and sustained levels in ELF above the target concentrations for the entire dosing interval. These findings support the 3g dose that is included in the ASPECT-NP Phase 3 trial.  (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Becky Jayakumar, PharmD College of Pharmacy Assistant Professor of Pharmacy Practice Roseman University of Health Sciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bacteremia (bloodstream infections) due to Gram-negative (GN) bacteria are a frequent cause of severe sepsis and pose serious therapeutic challenges due to multidrug-resistance (MDR). Ceftolozane/tazobactam (C/T) is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor. This retrospective, observational study evaluated the clinical outcomes of C/T real-world use in severely ill patients. Twenty-two patients with sepsis and/or bacteremia were included; 95% of whom had Pseudomonas aeruginosa that was resistant to almost all antibacterials with the exception of colistin. C/T successfully treated the majority of these complicated patients. In this real-world study, 77% of patients had a clinical response with C/T and 75% had a microbiological response. Clinical success rates were high and mortality rates were similar to other studies in this severely ill population. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Amanda Paschke, MD, MSCE Senior principal scientist Infectious disease clinical research Merck Research Laboratories MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study sought to evaluate a new beta-lactam/beta-lactamase inhibitor antibacterial combination, imipenem/relebactam (IMI/REL), compared with colistin plus imipenem for the treatment of infections caused by resistant Gram-negative bacteria. Patients enrolled in the trial had hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections (cIAI), or complicated urinary tract infections (cUTI) caused by pathogens that were non susceptible to imipenem, a carbapenem antibacterial. In this study, the primary outcome was a favorable overall response to treatment, which was comparable between the IMI/REL vs colistin + IMI arms. Colistin (often combined with a carbapenem) is currently among the standard of care treatment regimens for MDR infections.  A key secondary endpoint of the study was safety.  IMI/REL was well tolerated; among all treated patients, drug-related adverse events (AEs) occurred in 16.1% of IMI/REL and 31.3% of colistin + IMI patients with treatment-emergent nephrotoxicity observed in 10% (3/29 patients) and 56% (9/16 patients), respectively (p=0.002). Results of the trial support the use of imipenem-relebactam (IMI/REL) as an efficacious and well-tolerated treatment option for carbapenem-resistant infections.  (more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 02.05.2018

MedicalResearch.com Interview with: Dr. Michael F. Egan MD Merck & Co. North Wales, PA 19454   MedicalResearch.com: What is the background for this study? What are the main findings? Response: A leading theory of Alzheimer's Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer's Disease. EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer's Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer's Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment. Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.” Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, Leukemia, Merck, Transplantation / 12.12.2017

MedicalResearch.com Interview with: Francisco M. Marty, M.D Associate Professor, Harvard Medical School Dana–Farber Cancer Institute and Brigham and Women’s Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cytomegalovirus (CMV) is the most common infection in patients who undergo allogeneic hematopoietic-cell transplantation (bone marrow transplantation with cells from donors different than the patient). Up until now, we had no antiviral agent that could be used for prophylaxis (prevention) of CMV post-transplant because of the side effects of drugs available to date (ganciclovir, valganciclovir, foscarnet, cidofovir). This trial confirmed that letermovir was highly effective in preventing CMV infection when used in the first 100 days after allogeneic HCT, was associated with minimal side effects of concern and was also associated with lower all-cause mortality by Week 24 post-HCT. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Merck, Pharmacology / 18.10.2017

MedicalResearch.com Interview with: Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester MedicalResearch.com: What is the background for this study? What are the main findings? Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes. The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss. (more…)
Author Interviews, Cost of Health Care, Infections, Merck, Stem Cells, Transplantation / 12.10.2017

MedicalResearch.com Interview with: Dr. Jonathan Schelfhout, PhD Director, Outcomes Research Merck & Co. Inc. North Wales, PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The cost of hematopoietic stem cell transplantation has received increased attention after it was identified as a top 10 contributor to increasing healthcare costs in an AHRQ 2016 report. Many recent studies have explored the cost of HSCT but additional research is needed on the costly complications that can follow the transplant procedure. This research is particularly relevant for inpatient decision makers, as most transplant centers receive one bundled payment for the transplant and the treatment of any complications over the first 100 days. (more…)
Author Interviews, Boehringer Ingelheim, Columbia, Heart Disease, J&J-Janssen, Merck, NEJM / 14.09.2017

MedicalResearch.com Interview with: Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons MedicalResearch.com: What is the background for this study? What are the main findings? Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist - without aspirin - in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine. Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin. In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events. (more…)
Annals Internal Medicine, Author Interviews, Flu - Influenza, Merck, Technology / 11.09.2017

MedicalResearch.com Interview with: Jesse Papenburg, MD MSc FRCPC FRQS Clinical Research Scholar Assistant Professor of Pediatrics, McGill University Div. of Pediatric Infectious Diseases, Dept. of Microbiology Montreal Children’s Hospital Montreal, QC  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Influenza viruses cause yearly epidemics of acute respiratory illness affecting 5 to 30 percent of the population. Diagnosing influenza on the basis of only clinical symptoms is difficult because its manifestations vary and are nonspecific. Reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard for flu diagnosis, but these tests must be sent to a laboratory and have turnaround times that extend beyond the clinical encounter. Rapid and accurate diagnosis of influenza has the potential to improve patient outcomes and decrease health care costs. Since 2011, two novel classes of rapid influenza diagnostic assays i.e., with results available in <30 minutes, have been commercialized with claims of improved sensitivities based on technological improvements: 1) automated immunochromatographic antigen detection tests (digital immunoassays, DIAs) and 2) rapid nucleic acid amplification tests (NAATs). Our systematic review and meta-analysis synthesized the available evidence and compared the diagnostic accuracy of commercially available rapid tests for the detection of influenza A and B infection:
  • Overall, the rapid tests displayed very high specificities (≥98%). Physicians can therefore diagnose influenza with confidence on the basis of a positive RIDT, DIA, or rapid NAAT result.
  • The pooled sensitivities for DIAs (80.0% for influenza A and 76.8% for influenza B) and rapid NAATs (91.6% for influenza A and 95.4% for influenza B) are markedly higher than those for RIDTs (54.4% for influenza A and 53.2% for influenza B).
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AstraZeneca, Author Interviews, Eli Lilly, Merck / 07.09.2017

MedicalResearch.com Interview with: Dragana Radovanovic, MD  Head of AMIS Plus Data Center Hirschengraben Zürich MedicalResearch.com: What is the background for this study? What are the main findings? Response: What we know so far? When a woman suffers a heart attack she is older, has consequently more cardiovascular risk factors such as hypertension, has more comorbidities, is less likely to receive the same therapies and more likely to die in hospital. Furthermore, we know from many hospital statistics and administrative data bases that in-hospital mortality of acute myocardial infarction patients has been on the decrease from 1970 to the early 2000’s. We then wanted to know what the situation looks like in Switzerland and therefore analyzed in-hospital mortality over the last 20 years with regard to gender, age and therapies. For this study we used the data of the nationwide AMIS Plus registry (Acute Myocardial Infarction in Switzerland) which exists since 1997 and continuously prospectively collects clinical data of patients hospitalized with acute myocardial infarction. We have found that during the last 20 years (from 1997 to the end of 2016) in-hospital mortality of patients with acute myocardial infarction in Switzerland has halved. Although in-hospital mortality was consistently higher in women, overall age-adjusted mortality has decreased more prominently in women compared to men. Especially in patients aged below 60 years a significant decrease in in-hospital mortality was observed in women but not in men. (more…)
Author Interviews, Flu - Influenza, Kaiser Permanente, Merck, NEJM, Vaccine Studies / 10.08.2017

MedicalResearch.com Interview with: Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network  MedicalResearch.com: What is the background for this study?
  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP). This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.
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Author Interviews, HIV, J&J-Janssen, Merck, Pharmacology / 26.07.2017

MedicalResearch.com Interview with: Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA  MedicalResearch.com: What is the background for this study? What are the main findings?
  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).
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Author Interviews, HIV, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Dr. Pedro Cahn Chief of the infectious disease unit at Juan A. Fernandez Hospital Buenos Aires, Argentina, and ONCEMRK lead study investigator MedicalResearch.com: What is the background for this study? What are the main findings? The ONCEMRK Phase 3 study was conducted to evaluate the efficacy and safety of once-daily ISENTRESS (raltegravir) HD 1200 mg (given as two 600 mg oral tablets) compared to twice daily raltegravir 400 mg, each in combination therapy with emtricitabine plus tenofovir disoproxil fumarate in previously untreated adults with HIV-1 infection with levels of HIV-1 RNA ≥ 1,000 copies/mL.
  • Week 96 data showed:
    • 5 percent of the 531 patients taking once-daily raltegravir 1200 mg (2 x 600 mg) achieved viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to 80.1 percent of the 266 patients taking twice-daily raltegravir 400 mg, both in combination therapy with emtricitabine plus tenofovir disoproxil fumarate, with a treatment difference of 1.4 percent.
    • Increases in CD4+T-cell counts from baseline were comparable for the two treatment regimens, with an average increase of 261.6 cells/mm3 for once-daily raltegravir (1200 mg) and 262.2 cells/mm3 for twice-daily raltegravir (400 mg).
    • Efficacy was consistent across a variety of patient populations, including those with high viral load at baseline (HIV-1 RNA >100,000 copies/mL).
    • Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent of patients in both treatment arms, with 4/531 (0.8 percent) in the once-daily raltegravir (1200 mg) treatment arm, and 2/266 (0.8 percent) in the twice-daily raltegravir (400 mg) treatment arm through 96 weeks.
    • The rate of discontinuation of therapy due to adverse events through 96 weeks was low (1.3 percent in patients receiving once-daily raltegravir (1200 mg) and 2.3 percent in patients receiving twice-daily raltegravir (400 mg).
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Annals Internal Medicine, AstraZeneca, Author Interviews, Brigham & Women's - Harvard, Heart Disease, Merck, Pharmacology / 25.07.2017

MedicalResearch.com Interview with: Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events. However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, HIV, JAMA, Kaiser Permanente, Merck / 13.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised. We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Lipids, Merck / 19.06.2017

MedicalResearch.com Interview with: Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose. Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
Author Interviews, Merck, Pharmacology / 13.06.2017

MedicalResearch.com Interview with: Roy F Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A Professor, Department of Infectious Diseases, Director, Infection Control and Employee Health, Division of Internal Medicine Director of the clinical virology research program,Department of infectious diseases Infection control and employee health The University of Texas MD Anderson MedicalResearch.com: Would you briefly explain the significance of CMV infections? What is the background for this study? Response: Cytomegalovirus (CMV) is one of the most important causes of infectious complications following organ transplantation and is a significant cause of illness and death in patients who have undergone allogeneic hematopoietic cell transplantation (allo-HCT). For more than 20 years, we have been managing this infection and trying to develop effective strategies to control it, but to no one’s satisfaction; CMV infection is still associated with significant morbidity and mortality in this high-risk population. Most transplant centers have adopted preemptive antiviral therapy as the strategy of choice for HCT patients.1 While anti-CMV drugs have decreased the incidence of CMV diseases, their use for prophylaxis has not been associated with improved outcomes.1 Demographic and transplant trends heighten the need for new anti-CMV agents. In the U.S, 83% of people aged 60 and older are CMV seropositive. These older patients received 8% of all hematopoietic-cell transplants in 2000-2006, a figure that jumped to 22% in 2007-2013. As Baby Boomers age, many more allogeneic transplant patients will be CMV seropositive. Therefore, prophylactic antiviral compounds that could effectively control viral replication, and restrict some pathologic processes of CMV diseases, could potentially lessen the complications associated with CMV infection and possibly reduce all-cause mortality. (more…)
ASCO, Author Interviews, Breast Cancer, Merck, NYU / 10.06.2017

MedicalResearch.com Interview with: Sylvia Adams, MD Associate Professor of Medicine Breast Cancer and Cancer Immunotherapy Programs NYU Langone Medical Center Cancer Institute/Clinical Cancer Center New York, NY 10016   MedicalResearch.com: What is the background for the Keynote-086 trial ? What are the main findings? Response: This study is the largest immunotherapy study to date presented in metastatic triple negative breast cancer. This phase 2 trial studied the efficacy and safety of pembrolizumab (P) as single agent in a very aggressive disease and had two cohorts, a cohort of previously untreated patients (Cohort B) and a cohort with patients who had received prior chemotherapy lines in the metastatic setting (Cohort A). The study showed that single agent pembrolizumab can elicit durable responses in a subset of patients. This was found regardless of tumoral PD-L1 expression but appeared to be much more frequent in women without prior chemotherapy treatments in the metastatic setting. Survival is especially promising for patients responding to therapy. (more…)
Author Interviews, Infections, Merck / 08.06.2017

MedicalResearch.com Interview with: Sanjay Merchant, PhD Executive Director Center for Observational and Real-world Evidence (CORE) Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: In February, the World Health Organization (WHO) published its first ever list of antibiotic-resistant “priority pathogens” that pose the greatest threat to human health. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics, referred to as multidrug-resistant (MDR) bacteria, which have built-in abilities to find new ways to resist treatment. MDR Pseudomonas aeruginosa (MDR PsA) is listed as one of the pathogens in the Critical category in terms of need for new therapies. It poses an urgent threat. We set out to better understand the clinical and economic burden associated with hospital-onset MDR PsA so that appropriate treatment strategies can be employed to mitigate resistance. Our findings were presented at ASM Microbe 2017. Mortality rates for hospital-onset MDR PsA patients (20.1%) were almost twice as high compared to patients who did not have MDR PsA (11.5%). The MDR PsA patient group had a significantly higher odds ratio for mortality even after controlling for various factors that may impact mortality. Hospital-onset MDR PsA patients spent six additional days in the hospital when compared to patients who did not have MDR PsA infections. These findings highlight the public health threat of MDR PsA among hospitalized patients and the need for timely and effective therapy. (more…)
Author Interviews, Hepatitis - Liver Disease, Kidney Disease, Lancet, Merck / 01.06.2017

MedicalResearch.com Interview with: Annette Bruchfeld MD, PhD Senior Consultant Associate Professor Karolinska Institute Dept of Renal Medicine, M99 Karolinska University Hospital Huddinge Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: In patients with stage 4–5 chronic kidney disease(CKD), hepatitis C virus (HCV) infection can accelerate the decline in kidney function, impair health-related quality of life (HRQOL), and decrease survival chances of both patients and grafts in transplantation recipients. In this study additional data from patients with stage 4–5 chronic kidney disease undergoing treatment for HCV infection in the C-SURFER study, including HRQOL and resistance analyses was presented not previously reported for this patient population with gwnotype 1 infection. The final virological analysis of this study indicated a high cure rate with sustained virological response at 12 weeks after the end of treatment (SVR12) in more than 98% of all treated patients. Even in patients with resistance-associated substitutions (RASs) the SVR was high in 11 (84·6%) of 13 patients genotype 1a infection. (more…)
Author Interviews, Baylor College of Medicine Houston, Merck, Rheumatology / 07.05.2017

MedicalResearch.com Interview with: Grace H. Lo MD MSc Department of Medicine, Baylor College of Medicine Medical Care Line and Research Care Line, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety Michael E. DeBakey Medical Center, Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoarthritis is the most common form of arthritis. Many people who have signs of osteoarthritis on x-rays do not necessarily complain of pain. Presently, there are no known strategies for preventing the development of pain in this group of people. This study suggests that if these people have noisy knees (otherwise known as “crepitus”), they are at higher risk for developing pain within the next year compared to the people who do not have noisy knees. Future studies that target people who have x-ray signs of osteoarthritis, who do not complain of pain, but do report noisy knees, hold the promise of identifying interventions that can prevent knee pain. (more…)
Author Interviews, Biomarkers, Hepatitis - Liver Disease, Lancet, Merck / 25.04.2017

MedicalResearch.com Interview with: Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing. We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) - a point-of-care hepatitis C virus test that can detect active infection - from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Merck / 24.04.2017

MedicalResearch.com Interview with: Eilish McCann, PhD Director, Outcomes Research (Center for Observational and Real-World Evidence) Merck MedicalResearch.com: What is the background for this study? Response: One of the most pressing challenges facing medicine today is the emergence of bacterial resistance to antibiotics. One area of high concern is the increasing prevalence of resistance to powerful antibiotics like carbapenems, as patients with infections due to carbapenem-resistant bacteria have very few alternate effective treatment options. In this study we used real-world data from a Becton, Dickinson and Company electronic research data set to analyze over 140,000 bacterial isolates from patients at 342 hospitals across the United States, so that we could investigate where the burden of carbapenem resistance is most acute. Importantly analysis of real-world data in this way allows us to gain insights from a large number of hospitals, giving a broad and nationally representative picture of the resistance burden. (more…)
AstraZeneca, Author Interviews, Autism, Boehringer Ingelheim, Depression, Eli Lilly, J&J-Janssen, JAMA, Merck, OBGYNE / 17.04.2017

MedicalResearch.com Interview with: Florence Gressier MD PhD Insermk Department of psychiatry CHU de Bicêtrem Le Kremlin Bicêtre France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Results from recent studies have suggested an increased risk for Autism Spectrum Disorders (ASDs) in children exposed to antidepressants in utero. We performed a systematic review of and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception. Our systematic review and meta-analysis suggests a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. In addition, the association was weaker when controlled for past maternal mental illness. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for Autism Spectrum Disorders. (more…)
Author Interviews, Boehringer Ingelheim, Dermatology, Eli Lilly, Immunotherapy, J&J-Janssen, Merck / 30.03.2017

MedicalResearch.com Eric Hughes Global Development Franchise Head Immunology & Dermatology Novartis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psoriasis is a chronic immune-mediated inflammatory disease that negatively impacts patients’ quality of life (QOL); therefore QOL outcomes are increasingly recognized as an important measure of efficacy in psoriasis, complementing traditional measures of severity such as the Psoriasis Area and Severity Index (PASI). Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile. Biologic therapies for psoriasis have previously been associated with a fall-off in efficacy over time; accordingly, extended follow-up is required to adequately evaluate novel therapeutic strategies like IL-17A inhibition. Recently, results from the extension of the SCULPTURE secukinumab trial showed that high responses initially achieved with secukinumab at year 1 in the SCULPTURE study were sustained over time up to 3 years with no new or unexpected safety concerns. In this analysis, we examined whether the sustained efficacy observed in SCULPTURE up to 3 years was translated into sustained effect of secukinumab on patient’s QOL measured by the Dermatology Life Quality Index (DLQI) questionnaire. SCULPTURE, a multi-center extension study, was conducted with subjects who completed 52 weeks of treatment. Subjects were randomized into two maintenance dosing regimens; a fixed-interval schedule of secukinumab 300 mg every 4 weeks (Fixed interval dosing regimen (FI) cohort), and secukinumab retreatment-as-needed (Retreatment as needed (RAN) cohort), in which subjects received placebo until start of relapse, at which time secukinumab 300 mg every 4 weeks was re-initiated. The analysis using as-observed data showed that at Year 3, improvements in the total score on DLQI was well sustained in both FI and RAN cohorts. Approximately two-thirds of the subjects in the FI cohort reported no impact of skin disease on QOL (corresponding to a score of 0 or 1 on DLQI). The proportion of patients in the RAN cohort reporting no impact of the disease on their QOL was well sustained through 3 years but remained consistently lower than those observed in the FI cohort. The results for each subscale of the DLQI questionnaire were consistent with those with DLQI total score i.e. showing high and sustained proportions of patients reporting no impact of the disease on different domains of health-related QOL in the two secukinumab cohorts with greater effect in the FI cohort compared to the RAN cohort. (more…)