MassBiologics receives orphan drug status from FDA for hepatitis C treatment

PUBLIC RELEASE DATE: 4-Dec-2013

Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School

Monoclonal antibody designed to prevent hepatitis C recurrence in liver transplant patients

BOSTON, MA – MassBiologics of the University of Massachusetts Medical School (UMMS) has received an orphan drug designation from the U.S. Food and Drug Administration (FDA) for MBL-HCV1, a monoclonal antibody developed to prevent hepatitis C virus (HCV) recurrence in patients receiving a liver transplant.

Complications from chronic HCV infection are the most common indications for liver transplantation today. For patients with end-stage liver disease or hepatocellular carcinoma resulting from HCV infection, liver transplantation is often the only treatment option, but it is not a cure for the disease. In almost all cases, the new donor liver becomes infected with HCV soon after transplantation.

MassBiologics' monocloncal antibody, currently in a Phase 2 clinical trial, is intended to prevent HCV from damaging the transplanted liver.

"Being granted orphan drug status facilitates the goal of bringing this investigational product to patients," says Deborah C Molrine, MD, deputy director of clinical affairs at MassBiologics and professor of pediatrics at University of Massachusetts Medical School. "The economic incentives available to MassBiologics and potential commercial partners through the Orphan Drug Act will contribute greatly to bringing this monoclonal antibody to market as a treatment option for patients receiving liver transplants as a result of HCV infection."

The Orphan Drug Act was established by Congress in 1983 to aid the development of new therapies for rare medical conditions or diseases that affect less than 200,000 patients annually. To help stimulate new drug development for these less common conditions, the FDA provides financial benefits to companies that achieve orphan drug designation, including market exclusivity for 7 years, tax incentives, fee waivers and potential grant support.

Developed by MassBiologics, MBL-HCV1 is a fully human monoclonal antibody that targets a region of the hepatitis C virus on its surface envelope, preventing it from infecting liver cells. MBL-HCV1 has been shown to be safe in healthy human subjects and is currently being studied in patients with chronic hepatitis C infection undergoing liver transplantation.

"Infusions of the monoclonal antibody have been well-tolerated in transplant patients and allow for delivery of the targeted HCV treatment to begin just before the removal of the diseased liver and to continue through the early post-transplant period," said Dr. Molrine. "A Phase 2 study is underway in liver transplant patients that combines the monoclonal antibody with one of the first two oral HCV direct acting anti-virals to be licensed by the FDA. We anticipate having data to present soon on the effect of this treatment on HCV detection after liver transplantation."

###

About MassBiologics

MassBiologics, formerly known as the Massachusetts Biologic Laboratories, is the only non-profit FDA- licensed manufacturer of vaccines and other biologic products in the United States. MassBiologics produces 20-30 percent of the US tetanus/diphtheria vaccine supply. In addition to the HCV monoclonal antibody program, MassBiologics has discovered and developed human monoclonal antibodies to severe acute respiratory syndrome (SARS),Clostridium difficile and to rabies virus. MassBiologics traces its roots to 1894, and since then has maintained a mission to improve public health through applied research, development and production of biologic products. MassBiologics has been a part of the University of Massachusetts Medical School since 1997.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School (UMMS), one of five campuses of the University system, is comprised of the School of Medicine, the Graduate School of Biomedical Sciences, the Graduate School of Nursing, a thriving research enterprise and an innovative public service initiative, Commonwealth Medicine. Its mission is to advance the health of the people of the Commonwealth through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. In doing so, it has built a reputation as a world-class research institution and as a leader in primary care education. The Medical School attracts more than $240 million annually in research funding, placing it among the top 50 medical schools in the nation. In 2006, UMMS's Craig C. Mello, PhD, Howard Hughes Medical Institute Investigator and the Blais University Chair in Molecular Medicine, was awarded the Nobel Prize in Physiology or Medicine, along with colleague Andrew Z. Fire, PhD, of Stanford University, for their discoveries related to RNA interference (RNAi). The 2013 opening of the Albert Sherman Center ushered in a new era of biomedical research and education on campus. Designed to maximize collaboration across fields, the Sherman Center is home to scientists pursuing novel research in emerging scientific fields with the goal of translating new discoveries into innovative therapies for human diseases.

Source

Hope for liver patients

Thursday, March 31, 2011

UMASS SEEKS TO STOP TRANSPLANT RE-INFECTION

By Karen Nugent TELEGRAM & GAZETTE STAFF

WORCESTER — A new liver does not mean the end of hepatitis C.

The virus, which can go undetected for years, is the leading cause of liver failure in the United States, and for many patients, a transplant is the only life-saving treatment. But the hepatitis C virus circulates in the blood, and during transplant surgery, infected blood immediately gets into a donated liver.

“One-hundred percent (of transplanted livers) get re-infected,” said Dr. Donna M. Ambrosino, executive director of Massachusetts Biologic Laboratories, a division of the University of Massachusetts Medical School. “The virus stays in the blood for a couple of days, if not longer. You cannot be without your liver, and you can't put the new liver in without blood spilling on it and getting into it. So we're between a rock and a hard place.”

A re-infected liver, while giving patients perhaps five more years of life, she said, accelerates the course of the disease, and standard antiviral medications are not well-tolerated in transplant patients.

The medical school, along with five hospitals in Boston, New York and Connecticut, is entering the second phase of a clinical trial of a new treatment for the prevention of hepatitis C re-infection in liver transplant patients. The treatment, a monoclonal antibody, is different from the usual antiviral drugs in that it binds the virus and blocks its ability to get into the liver, Dr. Ambrosino said.

There are 10 patients currently in the study, with a target enrollment of 16 patients. Half are given the antibody, so far known only as MBL-HCV1, and half are given a placebo.

Dr. Ambrosino, who is also a professor of pediatrics at the medical school, said results will likely be available in the summer. If the virus is not found in patients 42 days after transplantation, it will be deemed a success. If the virus is found, a trial with a higher dose of antibody will begin.

The antibody — or the placebo — is administered to patients by infusion, in phases.

The first dose is given a few hours before transplant surgery, and another is given during surgery between when the diseased liver is removed and the donor liver is implanted. A third infusion is given just after surgery, followed by daily infusions during the first week of recovery. A final infusion is given on the 14th day after surgery.

A 2009 study of the antibody in 31 healthy volunteers showed no serious side effects.

Dr. Ambrosino said it generally takes 10 years of development and trials before a new medication becomes available.

According to the U.S. Centers for Disease Control and Prevention, hepatitis C virus infection is the most common chronic blood-borne infection in the United States, with approximately 3.2 million people chronically infected, and about 10,000 deaths per year. Of 6,000 or so liver transplants each year in the United States, half are the result of hepatitis C infection.

However, it is a slow-growing infection that may not show symptoms for 20 years — until liver failure becomes apparent, or abnormal laboratory tests are found.

Dr. Ambrosino said because the average age of a hepatitis C patient is 55 — smack in the middle of the baby boomer generation — they will probably make up the next wave of patients.

“So that's a large group, and there will be more people needing liver transplants,” she said.

While many boomers unknowingly carry the virus, Dr. Ambrosino said it is not entirely because of bad behavior such as drug use and multiple sex partners in the 1970s.

Hepatitis C can be transmitted through drug use via contaminated needles, and rarely through sexual contact, but she said the majority of cases were contracted through blood transfusions prior to the late 1970s when the virus was first identified. Since 1990, all donated blood has been tested for hepatitis C.

“It was not known in the '70s,” Dr. Ambrosino said.

The virus differs from hepatitis A, a largely food-borne illness, and hepatitis B, a more obvious illness, which is also transmitted through blood but was identified earlier and for which there is a vaccine.

The Massachusetts Biologic Institute was part of the state Department of Public Health until 1997, when it became aligned with UMass. Its main focus is public health — especially infectious diseases — and its major source of revenue is manufacturing tetanus-diphtheria vaccine and other medications. Monoclonal antibodies are the latest products, Dr. Ambrosino said.

Contact Karen Nugent via email at knugent@telegram.com

Source

First liver transplant patients receive experimental drug to prevent hepatitis C infection

Public release date: 18-Jan-2011

Contact: Michael Cohen
michael.cohen@umassmed.edu
508-868-4778
University of Massachusetts Medical School

Phase 2 clinical trial begins for a novel monoclonal antibody

Boston, Mass. — Following a successful Phase 1 study for safety, researchers at MassBiologics of the University of Massachusetts Medical School (UMMS) today announced the beginning of a Phase 2 clinical trial testing the ability of a human monoclonal antibody they developed to prevent hepatitis C virus (HCV) infection of a donor liver in transplant patients.

The first patients were enrolled in the study in December. The primary goal of this randomized, double-blind, placebo-controlled study is to test if the monoclonal antibody, designated MBL-HCV1, prevents re-infection of patients chronically infected with HCV who are undergoing liver transplantation.

MassBiologics plans to enroll 16 patients in the first part of the study. "We are hopeful that positive results from this study will meet an important public health need, and we could not take this important step without the willing and thoughtful participation of these volunteers," said Donna Ambrosino, MD, executive director of MassBiologics and a professor of pediatrics at the Medical School.

There are currently five hospitals participating in the trial—Massachusetts General Hospital, Beth Israel Deaconess Medical Center, both in Boston, Lahey Clinic in Burlington, Massachusetts, Yale-New Haven Hospital in Connecticut and Mount Sinai Hospital in New York City—and others may join in the coming months. The first six patients enrolled have come from three of these sites.

HCV damages the liver and is the leading indication for liver transplantation, diagnosed in about half of the 6,000 patients who receive liver transplants each year in the United States. According to the US Centers for Disease Control and Prevention, 3.2 million Americans are chronically infected with HCV and approximately 10,000 die annually of the disease. Globally, as many as 170 million people are estimated to suffer from HCV infection.

For patients with end-stage liver disease from HCV infection, liver transplantation is the only option. While it can be a life-saving treatment, transplantation does not cure the disease. In nearly all cases, the patient's new liver is eventually infected by HCV because the virus remains in the patient's bloodstream during surgery. The course of recurrent HCV disease is accelerated after transplantation and up to 20 percent of transplant patients develop cirrhosis within five years. Unfortunately, the standard antiviral drugs currently used to treat HCV prior to the onset of end-stage liver disease are poorly tolerated after liver transplantation, leaving these patients with few options.

To address this unmet medical need, the team at MassBiologics, working in collaboration with investigators Gyongyi Szabo, MD, PhD, professor of medicine, and Robert Finberg, MD, professor and chair of the Department of Medicine at UMMS, set out to develop a human monoclonal antibody that could clear HCV from a patient's bloodstream and protect the donated liver from infection. In pre-clinical studies, MBL-HCV1 successfully neutralized the virus in cell culture and animal models of infection. A Phase 1 study in 31 healthy volunteers completed in 2009 showed the antibody was well tolerated, with no serious side effects. The Phase 1 study also measured the levels of the antibody in the bloodstream and its ability to bind and inactivate the virus, thereby helping to establish the dosage and protocol for the Phase 2 study now under way.

In the current study, patients will be randomized to receive an infusion of either the antibody or placebo between one and four hours prior to surgery. Then, during the phase of surgery when the diseased liver is removed, but before the donor liver is implanted, patients will receive a second infusion of either the antibody or placebo. After the surgery is completed, the patients will receive a third infusion, and then daily infusions during the first week of recovery. A final infusion is administered on the 14th day after liver transplantation.

"The liver is the main reservoir for the hepatitis C virus," said Brett Leav, MD, senior director of clinical affairs at MassBiologics. "The virus circulates in the blood, but only resides and replicates in the liver. So the idea here is to clear the virus from the bloodstream before it has an opportunity to re-infect the new liver."

After transplantation, patients' blood will be tested on a regular basis to screen for reemergence of HCV, which is usually detected within the first week after transplantation. The primary goal of the Phase 2 trial is to see if the patients who received the antibody are free of HCV at 42 days after transplantation. An interim analysis is planned after the first 16 patients have been enrolled in the trial, and a Data Safety and Monitoring Board overseeing the study will assess the effectiveness and safety of MBL-HCV1.

###

About MassBiologics

MassBiologics, also known as the Massachusetts Biologic Laboratories, is the only non-profit FDA- licensed manufacturer of vaccines and other biologic products in the United States. MassBiologics produces 30 percent of the US tetanus/diphtheria vaccine supply. In addition to the HCV program, MassBiologics has discovered and developed human monoclonal antibodies to severe acute respiratory syndrome (SARS), and to Clostridium difficile (C. difficile), which has shown efficacy in a Phase 2 clinical trial, and to rabies which will be starting Phase 2 clinical trial soon in collaboration with the Serum Institute of India. MassBiologics traces its roots to 1894, and since then has maintained a mission to improve public health through applied research, development and production of biologic products. MassBiologics has been a part of the University of Massachusetts Medical School since 1997.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $255 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit http://www.umassmed.edu/.

Source