Introduction of CHB
Chronic HBV infection affects over 257 million people globally and leads to cirrhosis and liver cancer. Prevalence varies greatly with geographic locations. In areas where the prevalence is high, such as Southeast Asia, China, and Africa, more than half the population is infected at some time in their lives.
HBV is an enveloped, partially double-stranded DNA virus. It is transmitted percutaneously, sexually, and perinatally. HBV infection symptoms including fatigue, malaise, nausea, abdominal pain, dark urine, and jaundice will occur from 30 days to 6 months after the exposure.
The diagnosis of HBV infection requires the evaluation of several biomarkers including hepatitis B surface antigen (HBsAg), anti-HBs, hepatitis B core antibody (IgM and IgG), hepatitis B e antigen (HBeAg) and anti-HBe. Serum hepatitis B surface antigen (HBsAg) is a marker of HBV infection, and antibodies against HBsAg signify recovery. A serum marker of active viral replication, hepatitis B e antigen (HBeAg), is accompanied by serum levels of HBV DNA. The presence of HBsAg indicates that the person is infected by the virus.
Hepatitis D virus has a circular ribonucleic acid (RNA) genome that requires polymerases and proteases of HBV for replication. In the process of replication, HDV needs HBV surface antigen (HBsAg) to coat its HDV infection occurs only simultaneously or as super infection with HBV.
Approximately 15 million people across the world are chronically co infected with HDV and HBV. HDV is distributed worldwide with more than 24% of HBV carriers with HDV markers be identified in Africa, Southwest Asia and the Mediterranean basin. In the United States, HDV prevalence is lower, ranging from > 1 to 10%.
Compared with infection with HBV alone, HDV co-infection with H BV is associated with a higher rate of hepatitis in an acute infection and HDV superinfection in individuals with chronic HBV infection can lead to more severe progressive chronic liver disease.
Unmet Medical Needs
Long acting interferon is an important and effective medication in hepatitis treatment extensively. It can stimulate the liver to produce a special protein, which can inhibit the entry of hepatitis B virus into liver cells and its replication in liver cells, and reduce the damage to liver cells. P1101 is an optimized form of long acting interferon that allow for convenient once every 2 weeks dosing that is conductive to higher patient treatment compliance and willingness with lower side effect and higher safety compare to traditional long acting interferon, and it is expected to be helpful in slowing down or stopping the progression of hepatitis B or hepatitis D. If this goal can be achieved, it will decrease financial burden of patients and government.
Incentive of the Trial
Hepatitis B is a serious and stubborn infectious disease and has been identified as the main cause of cirrhosis and hepatitis. The P1101 of PharmaEssentia product is better than conventional interferons with fewer AEs, high safety and given every two weeks in Phase II study results. Phase Ib study of sequential administration of P1101 and anti-PD1 for chronic hepatitis B or D infection treatment is ongoing. If the trail is successful for HBV or HDV treatment, P1101 + anti-PD1 treatment regimen is expected to control or even eliminate HBsAg, it has the opportunity to provide new therapeutic guidelines and directions for the treatment of HBV or HDV.