Inovio Pharmaceuticals, Inc. announced that interim phase 1 results show its DNA immunotherapy designed to treat hepatitis B virus (HBV) infection was safe, well-tolerated and generated virus-specific T cells, including CD8+ killer T cells, meeting the objectives of the clinical study.
Preliminary immunology data from the trial revealed that treatment of patients with INO-1800 resulted in the generation of T cells that recognized key components of the hepatitis B virus and reacted by making antiviral cytokines such as Interferon gamma, a protein believed to be linked to clearance of HBV from the liver. INO-1800 was also able to activate and expand CD8+ killer T cells that displayed markers believed to be important for retention in the liver as well as multiple potential mechanisms for killing virally infected cells.
Dr J Joseph Kim, Inovio’s president & CEO, said, “Our hepatitis B immunotherapy trial results clearly demonstrate the potential of INO-1800 as an immunotherapy for this widespread infection that is a major cause of liver cancer. Key to my optimism is that INO-1800 drove generation of HBV-specific killer T cells across all cohorts. We see INO-1800 as a key immunotherapy component of an effective anti-HBV combination therapy. We have had discussions with several potential partners and expect to further advance this product via collaboration or partnership.”
Although there is an effective prophylactic vaccine available to prevent infection, more than 240 million people are living with chronic HBV infection globally, and the disease is causing more than one million deaths annually. Currently available antiviral treatments are not adequate to clear this infection and may only slow progression of the disease. HBV can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer. These latest results from our Phase 1 trial indicate that treatment with INO-1800 is generating the type of immune response considered to be key in the treatment of chronic hepatitis B infection using an immunotherapy.
This open-label, dose escalation study evaluated the safety, tolerability, and immunogenicity of INO-1800, alone or in combination with INO-9112, Inovio's IL-12-based immune activator, in 90 adults with chronic hepatitis B infection. The primary endpoints were safety and tolerability. The secondary endpoints evaluated the cellular and humoral immune response to INO-1800 and investigated the therapy's effect on several viral and antiviral parameters. All trial subjects, including the ones in the control group, were also medicated with standard-of-care oral antiviral therapies during the study. Inovio plans to report additional data from this trial at upcoming scientific conferences and in a publication.
In a previously published preclinical study, Inovio researchers found the vaccine-specific T cells exhibited a killing function, and could migrate to and stay in the liver and cause clearance of target cells without evidence of liver injury. This animal study was the first study to provide evidence that intramuscular immunization can induce killer T cells that can migrate to the liver and eliminate target cells, demonstrating the potential of this immunotherapy.
Chronic infection with hepatitis B virus is one of the major causes and risk factors for liver cirrhosis and liver cancer. The virus is very infectious– 100 times more so than HIV – with over 240 million people chronically infected worldwide. More than 60 million of these people are at risk of the major complications of liver cirrhosis and liver cancer, which cause over 700,000 deaths globally each year. Liver cancer is the third most common cancer and the most deadly, killing most patients within five years of diagnosis.
Inovio is taking immunotherapy to the next level in the fight against cancer and infectious diseases. Inovio the only immunotherapy company that has reported generating T cells in vivo in high quantity that are fully functional and whose killing capacity correlates with relevant clinical outcomes with a favourable safety profile.