Friday, May 29, 2015

Phase I/II Opdivo (nivolumab) Trial Shows Bristol-Myers Squibb’s PD-1 Immune Checkpoint Inhibitor is First to Demonstrate Anti-Tumor Activity In Patients With Hepatocellular Carcinoma

  • Interim results show favorable safety profile of Opdivo, and durable responses in previously-treated patients
  • Overall survival rate of 62% at 12 months observed at this interim analysis
  • Hepatocellular carcinoma is the second most frequent cause of cancer-related death worldwide and remains an area of significant unmet medical need
  • Patients with hepatocellular carcinoma who have relapsed or have disease progression, following standard of care, have a median survival with best supportive care of ~7 to 8 months

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from an interim analysis of CA209-040, a Phase I/II dose-ranging trial evaluating the safety and anti-tumor activity of Opdivo (nivolumab) in previously-treated patients with hepatocellular carcinoma (HCC) or advanced liver cancer. Initial findings demonstrated that the estimated survival rate in evaluable patients (n=47) was 62% at 12 months. Results also show the safety profile of Opdivo is generally consistent with that previously-reported for Opdivo in other tumor types. These data will be featured today, May 29, during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) press briefing at 1:00 – 2:00 p.m. CDT and presented on Saturday, May 30 from 8:27 a.m. – 8:39 a.m. CDT (Late Breaking Abstract #101).

“Hepatocellular carcinoma is an aggressive and fatal cancer, comprising 90 percent of all liver cancer in adults worldwide with limited therapeutic options for patients with advanced stage disease; no treatment advances have been made for patients who fail to respond or progress on the current standard of care,” said Anthony B. El-Khoueiry, MD, lead study author and associate professor of clinical medicine and phase I program director at the University of Southern California Norris Comprehensive Cancer Center. “These preliminary data are encouraging and support the ongoing evaluation of nivolumab in this patient population, as they show promising preliminary survival data, and durable partial or complete response in one out of five nivolumab-treated patients, with many others experiencing stable disease.”

More than 700,000 people around the world are diagnosed with HCC each year with a majority of all HCC cases caused by infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV), making HBV/HCV the most common risk factor for liver cancer worldwide. Patients with advanced HCC receiving the current standard of care have a median overall survival of less than 1 year. For patients who have relapsed or have disease progression, median survival with best supportive care is approximately 7 to 8 months.

“Bristol-Myers Squibb’s experience in hepatitis and Immuno-Oncology make us poised as leaders to advance Opdivo into additional studies of hepatocellular carcinoma,” said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. “Opdivo has demonstrated improvements in survival in a number of different tumor types. We are excited that this trial has shown the potential that this may extend to advanced liver cancer and hope to confirm these findings in future trials.”

About the CA209-040
CA209-040 is a Phase I/II dose-ranging trial that evaluated the safety and anti-tumor activity of Opdivo in patients with HCC, the majority of whom had received prior treatment. The trial included 47 HCC patients who were enrolled into one of three treatment arms depending on whether or not they were infected with HCV or HBV. Patients enrolled in the trial received Opdivo doses ranging from 0.1 – 10 mg/kg intravenously every 2 weeks for up to 2 years. The primary objective was safety, tolerability, dose limiting toxicities, and maximum tolerated dose. Anti-tumor activity was a secondary objective (using RECIST 1.1 criteria), and overall survival was an exploratory objective.
As of this interim analysis, 62% of patients in the study were still alive after 12 months. Eight (19%) patients (of 42 evaluable patients) achieved a complete or partial response, meaning that the size of their tumors measured at baseline decreased by 30–100% with Opdivo treatment. In patients with response, duration of response ranged from more than 1.4 – 12.5 months. Seventeen patients remained on study treatment and 30 discontinued treatment due to progressive disease (n=26), complete response (n=2), or adverse events (n=2).

CA209-040 is the first trial to characterize the safety profile of Opdivo monotherapy in patients with HCC, including those with HCV and HBV infections. In the trial, safety and tolerability were well-characterized, with the frequency and intensity of treatment-related adverse events (AEs) being consistent across Opdivo dose levels. The majority of side effects were mild to moderate in nature with abnormal liver enzymes (19% AST and 15% ALT), rash (17%) and elevation of amylase (15%) and lipase (17%) being the most common; the abnormal liver enzymes and elevated amylase and lipase were not accompanied by any significant clinical symptoms. Grade 3–4 treatment-related AEs were infrequent (19%). There were no treatment-related deaths reported.

About Opdivo
Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the U.S., the U.S. Food and Drug Administration (FDA) granted its first approval for Opdivo for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo received its second FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Read complete press release here

Wednesday, May 27, 2015

GlobeImmune Announces Top Line Results From GS-4774 Phase 2 Trial in Virally-Suppressed Chronic HBV Patients

LOUISVILLE, CO–(Marketwired – May 27, 2015) – GlobeImmune, Inc. (NASDAQ: GBIM) today announced top line results from the GS-4774 Phase 2 study in patients with chronic hepatitis B on long term viral suppression with an oral antiviral treatment. In this study, patients treated with the highest dose of GS-4774 plus ongoing oral antiviral therapy (OAV) did not show a reduction in hepatitis B surface antigen (HBsAg) at week 24, the primary endpoint of the study, but at 48 weeks had a mean -0.17 log10 reduction of HBsAg compared with a -0.04 log10 reduction in the OAV alone group (p=not significant). Three patients receiving the highest dose of GS-4774 had HBsAg reductions between -0.94 and -3.89 log10 at 48 weeks. There was no difference in HBsAg reductions between the two lowest dose groups versus the control arm at 48 weeks. Further characterization of the T cell response to GS-4774 and association with HBsAg changes are ongoing.

GS-4774 was found to be generally safe and well tolerated, with injection site reactions identified as the primary adverse event. Data from this trial are expected to be submitted for future presentation and publication.

“We believe that this first Phase 2 trial of GS-4774 in virally-suppressed patients suggests initial biologic activity at the highest dose tested,” said Timothy C. Rodell, M.D., FCCP, President and CEO of GlobeImmune, Inc. “We look forward to collaborating with our partner Gilead Sciences, Inc. to identify potential next steps for GS-4774 in this patient population as well as to seeing the results from the second ongoing Phase 2 trial of GS-4774 in HBV treatment-naïve patients.”

About the 0101 TrialThe 0101 Phase 2 trial was designed to investigate GS-4774 in combination with ongoing oral antiviral treatment in patients with chronic HBV infection whose disease is currently under control with an oral antiviral therapy. The 0101 trial was a multicenter, multinational trial that enrolled 178 patients in a randomized, open-label design comparing three different doses of GS-4774 (2YU, 10YU or 40YU, with one YU equal to 10 million yeast cells), administered in combination with oral antiviral therapy versus antiviral treatment alone. [www.clinicaltrials.gov; NCT01943799]

About Chronic Hepatitis B Infection and the GS-4774 Tarmogen®
Chronic HBV is the most common serious liver infection in the world affecting approximately 400 million people. While approximately 80% of acutely infected patients clear the virus without treatment predominantly through a T cell immune response, there is currently no cure for the vast majority of chronically-infected patients. Untreated chronic HBV infection is associated with significant increase in related diseases, including liver cirrhosis, hepatic decompensation and liver cancer. Mortality is also increased for patients with chronic HBV infection, with 25-40% of patients dying from complications of liver disease.

GS-4774, exclusively licensed to Gilead Sciences, Inc., is a therapeutic vaccine engineered to activate an HBV-specific T cell immune response to eliminate, or clear virus from, cells containing HBV. The GS-4774 Tarmogen expresses a fusion protein utilizing sequences of the hepatitis B virus contained in the four major HBV genotypes worldwide. GS-4774 is being developed to increase the HBsAg seroconversion rate or cure, when used in combination with oral antiviral therapy.

Read complete press release here

Tuesday, May 26, 2015

Mortality from HCC, liver disease increases in patients with HBV

Patients in France positive for chronic hepatitis B virus infection had increased mortality due to chronic liver disease, hepatocellular carcinoma or non-Hodgkin lymphoma compared with the general population, according to data published in the Journal of Hepatology.

“In France, about 3 million people have been in contact with HBV, and 280,800 have chronic HCV infection,” the researchers wrote. “Hepatitis B-related mortality in developed countries is not well-known.

The aim of this study was first to evaluate the risk of mortality in a population-based cohort of people with chronic HBV infection compared with the general population, and second to identify predictors of all-cause mortality and HBV-related mortality.


Saturday, May 23, 2015

Understanding people with liver disease

Buena Bariring was just 18 when she had the biggest surprise of her life: While applying for a job, the nurse in charge of her medical examination revealed to her that she tested positive for hepatitis B.

“That time, I did not know the impact of that finding. In fact, it surprised me considering that since childhood, I was never seriously ill or felt anything wrong with me,” Bariring said.

It was the start of her ordeal as she found out that having hepatitis B was like being handed a death sentence. “I can’t continue my studies as I have no money. But then, I can’t land a decent job because of my health condition. The few companies who hired me assigned me to a job where I would have the least human contact,” lamented Bariring who is now a member of Yellow Warriors Society Philippines, an organization dedicated to fighting all forms of discrimination against hepatitis B and C carriers, and diminishing suffering from them through advocacy, research, education and service.


Monday, May 18, 2015

Additional Hepatitis-B Booster Required in Children with Coeliac Disease: Presented at ESPID

LEIPZIG, Germany -- May 18, 2015 -- Children with Coeliac disease have an impaired response to hepatitis-B virus (HBV) vaccine, and a single booster dose of HBV vaccine is not effective to achieve an adequate immune response, according to results from a prospective, observational study reported at the 33rd Annual Meeting of the European Society of Paediatric Infectious Diseases (ESPID).

“Several studies described an impaired immunological response to HBV vaccine in children with Coeliac disease, where a high percentage of nonresponders has been observed,” stated lead author Maria José Pérez MD, Henares Universitary Hospital, Coslada, Spain, speaking here on May 15.

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Thursday, May 14, 2015

Guidelines for Hepatitis B Screening in Cancer Updated by ASCO

(HealthDay News) — Guidelines for hepatitis B virus (HBV) screening among patients with cancer have been updated, according to a special article published online May 11 in the Journal of Clinical Oncology.

Jessica P. Hwang, MD, from the University of Texas MD Anderson Cancer Center in Houston, and colleagues provide an updated provisional clinical opinion based on the American Society of Clinical Oncology panel consensus for HBV screening.


The authors note that patients should be screened for HBV infection before starting anti-CD20 therapy or hematopoietic cell transplantation. Patients with risk factors for HBV infection should also be screened. Screening should include hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), using the total anti-HBc or anti-HBc immunoglobulin G test. Antiviral therapy for HBsAg-positive/anti-HBc-positive patients should be started before or simultaneously with cancer therapy; HBsAg-negative/anti-HBc-positive patients should be monitored for reactivation with HBV DNA and alanine aminotransferase levels and treated with antivirals if reactivation occurs. For HBsAg-negative/anti-HBc-positive patients anticipating cancer therapies associated with a high risk of reactivation, clinicians can initiate antivirals, or they can monitor patients and initiate on-demand antivirals. HBV screening is not supported for patients who have neither HBV risk factors nor anticipate cancer therapy associated with a high risk of reactivation.

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Variations in Liver Cancer Attributable to Hepatitis Virus Variations

Discovery that hepatitis B and C viruses generate markedly different clinical pathologies highlights potential change in treatment plans for newly diagnosed patients

Newswise — CHICAGO —Significant clinical variations exist among patients with the most common type of liver cancer called hepatocellular carcinoma (HCC), depending on the viral cause of the disease –hepatitis B virus (HBV) or hepatitis C virus (HCV). These differences suggest that hepatitis status should be considered when developing treatment plans for newly diagnosed patients, according to researchers at The University of Texas MD Anderson Cancer Center.

These findings, from the largest single-center studies of its kind will be presented on Sunday, May 31 in an oral presentation at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO). The research builds on previous studies of differential effects of demographics, geographical distribution and risk factors, including hepatitis status, on treatment outcomes among patients with inoperable HCC. In these earlier studies, researchers observed different outcomes based on demographics and geographic patients distribution (Asia versus Europe and USA) among patients receiving the same local or systemic therapy approaches. They hypothesized that these differences might be attributed to variations with regard to hepatitis type, among other factors.

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