Altimmune Announces IND Clearance for a Phase 2 Trial of HepTcell™ Immunotherapeutic for the Treatment of Chronic Hepatitis B
GAITHERSBURG, Md., June 22, 2020 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to conduct a Phase 2 trial of HepTcell, a peptide-based immunotherapeutic for the treatment of chronic hepatitis B. The Company is also filing clinical trial applications in Canada, Spain, Germany and the United Kingdom. Altimmune plans to initiate a multinational trial in Q4 of this year, subject to an ongoing assessment of the impact of COVID-19 on study conduct.
“We are pleased to have obtained IND clearance for the evaluation of HepTcell in a Phase 2 trial. HepTcell is the only investigational immunotherapeutic designed specifically to restore antiviral T cell responses against the most conserved antigenic domains of the Hepatitis B virus (HBV),” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “We believe that HepTcell could also be the key immunotherapy component of a future anti-HBV combination regimen to help break immune tolerance and achieve a functional cure.”
According to World Health Organization estimates, chronic HBV affects 292 million worldwide, and nearly 900,000 people die annually of complications of the disease. There is no cure for chronic HBV, and currently available antiviral medications only control the disease and require life-long treatment. These treatments represent a significant burden for chronic hepatitis B patients, considering life-long commitment to medication and monitoring costs. If left untreated, chronic HBV infection can lead to serious health issues including cirrhosis, liver failure and liver cancer.
HepTcell is an immunotherapeutic product candidate composed of nine synthetic HBV-derived peptides formulated with IC31®, a TLR9-based adjuvant from Valneva SE. The HBV peptides were designed to drive T cell responses against all HBV genotypes in patients of diverse genetic background. In the Phase 1 clinical study conducted in the United Kingdom and South Korea, three monthly injections at two dose levels of HepTcell peptides were given with and without IC31® adjuvant as add-on therapy to entecavir or tenofovir in patients with Hepatitis B e-antigen (HBeAg)-negative chronic infections. All arms were generally well-tolerated and both high and low doses of HepTcell given in combination with IC31® resulted in potent T cell responses against HBV antigens – representing a break in immune tolerance with no evidence of immune-mediated adverse events.
Acute HBV infections are cleared through a T cell-dependent immune response. However, in chronically infected patients, high viral antigen load can induce a state of immune tolerance that prevets T cells from clearing the infection. Breaking immune tolerance is considered essential to achieving a functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) in the blood. Ultimately, the goal of all HBV therapeutics in current development is to achieve a functional cure by reactivating the T cell immune response and overcoming immune tolerance, either indirectly by further lowering HBV antigen load or directly, as is the goal of HepTcell.
The double-blind, randomized, placebo-controlled Phase 2 study of HepTcell plans to recruit 80 adult subjects with HBeAg-negative chronic HBV infection and low HBsAg levels. This patient population was selected as it is envisioned to mimic the HBV status of the patient population when HepTcell is combined with a novel direct-acting antiviral in subsequent trials. HepTcell will be administered intramuscularly at intervals of 4 weeks for 6 doses. The primary endpoint will be the virological response, defined as a 1-log reduction in HBsAg levels; secondary endpoints will incorporate safety, immunologic criteria, and other assessments of virologic response.
“HepTcell is a novel immunotherapeutic in development that holds potential for the treatment of patients with chronic hepatitis B,” said Dr. Mark Thursz, Professor of Hepatology and Head, Department of Metabolism, Digestion and Reproduction, Imperial College London and Lead Investigator of the multinational trial. “Immune tolerance is a considerable problem in chronic HBV patients, and I see the potential for HepTcell to be combined with the newer direct acting agents in development. HepTcell, if approved, could offer an additional agent in our efforts to achieve functional cure”.