GAITHERSBURG, Md.—Altimmune, Inc. has reported the first patient enrolled in its multinational Phase 2 clinical trial of HepTcell, a novel peptide-based immunotherapeutic under development for treatment of chronic hepatitis B (CHB). HepTcell is composed of nine synthetic hepatitis B virus (HBV)-derived peptides formulated with IC31, a TLR9-based adjuvant from Valneva SE. The HBV peptides are designed to drive T cell responses against all HBV genotypes in patients of diverse genetic backgrounds.
“As one of the most common infectious diseases worldwide, there remains a significant unmet medical need for improved CHB therapies, as currently approved therapeutics prevent disease progression but rarely lead to a functional cure,” stated Dr. Scott Harris, chief medical officer of Altimmune. “We believe the T cell immune intolerance that characterizes the disease must be broken for the development of a functional cure.”
Acute hepatitis B infections are cleared through a T cell-dependent immune response, but in chronically infected patients the high viral antigen load can induce a state of immune tolerance that prevents T cells from clearing the infection. Restoring T cell function 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 is to achieve a functional cure by reactivating the T cell immune response and overcoming immune tolerance.
The Phase 2 study — conducted in the US, Canada, and Europe — is a double-blind, randomized, placebo-controlled study of 80 adult patients with hepatitis B e-antigen (HBeAg)-negative inactive CHB and HBsAg ≤ 100 IU/mL. HepTcell will be administered in 6 doses at 4-week intervals for 24 weeks, and patients will be followed for one year to evaluate safety and durability of response.
The primary efficacy endpoint of the trial is virological response, defined as a 1-log reduction in HBsAg levels from baseline at 24 weeks. Secondary efficacy endpoints include reactivation of anti-HBV T cell responses, HBsAg clearance, and other assessments of virologic response.
“As a novel immunotherapeutic, HepTcell works by restoring dormant T cells to eliminate infection. While novel direct-acting agents under development — such as small inhibitory RNAs and capsid assembly modulators — have shown promise in reducing HBsAg load below 100 IU/mL, these agents have not resulted in the reactivation of T cell immunity and are unlikely to achieve durable virologic responses as monotherapies,” Harris continued. “Based on the encouraging preclinical and clinical data we are optimistic that HepTcell may be ideal in combination with novel direct-acting antivirals to achieve a functional cure for this disease.”
In a Phase 1 clinical study of HepTcell conducted in the UK and South Korea, three monthly injections at two dose levels of HepTcell peptides were administered both with and without IC31 adjuvant as add-on therapy to entecavir or tenofovir in patients with HBeAg-negative chronic infections. All doses of HepTcell 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.
In other Altimmune news, the FDA recently issued a clinical hold on Altimmune’s Investigational New Drug (IND) application for AdCOVID, a single-dose intranasal COVID-19 vaccine candidate. The FDA requested certain protocol modifications and the submission of additional chemistry, manufacturing, and controls data. However, Altimmune doesn’t anticipate that this news will have a significant impact on their clinical development timeline — the company has responded to the FDA’s hold letter from December 22, agreeing to each of the letter’s requests.
“We appreciate the FDA’s support and guidance as we seek to bring a novel, single-dose intranasal COVID-19 vaccine candidate into the clinic,” added Vipin K. Garg, president and CEO of Altimmune, in a press release. “We look forward to working with the FDA and will continue preparing to commence our planned Phase 1 clinical trial of AdCOVID.”