Combination therapy with the nucleic acid polymer REP 2139 and pegylated interferon alfa-2a was safe and had a similar tolerability compared with pegylated interferon alfa-2a monotherapy in patients with hepatitis B and hepatitis D coinfection, according to a recently published study.
“The primary clinical challenge for coinfection as well as HBV monoinfection is that, if you do your job to get rid of both infections, you have to be sure that the immune response you leave behind is capable of controlling the hepatitis B infection,” Andrew Vaillant, PhD, chief scientific officer at Replicor and study investigator told Healio.com/Hepatology. “If you control the hepatitis B infection, you also control the delta infection.”
REP 2139 is designed to block the release of subviral particles and establish functional control of serum HBsAg. In the REP 301 safety and tolerability phase 2 study, Vaillant and colleagues enrolled 12 patients with HBV/HDV coinfection.
Patients received 15 weeks of REP 2139 monotherapy, followed by 15 weeks of combined REP 2139 and PEG-IFN a-2a therapy, then 33 weeks of PEG-IFN a-2a monotherapy. One patient discontinued prior to the 33 weeks of interferon monotherapy due to an adverse event but completed follow-up.
Treatment-related adverse events included: anemia (n = 2), neutropenia (n = 8), thrombocytopenia (n = 10), raised alanine aminotransferase levels (n = 5), raised aspartate aminotransferase levels (n = 4) and increased bilirubin concentrations (n = 2). No serious adverse events were associated with treatment.
The elevated ALT and AST levels occurred with introduction of PEG-IFN a-2a and were substantially more pronounced in HBsAg rapid responder patients with HBsAg concentrations less than 1 IU/mL. Otherwise, the elevations were asymptomatic and self-resolving.
At the end of 24 weeks of REP 2139 monotherapy and combined therapy, six patients had HBsAg levels less than 50 IU/mL. Five of those patients maintained HBsAg control at the end of 1-year follow-up. Nine patients had HBV DNA levels less than 10 IU/mL at the end of 24 weeks of treatment and eight had no detectable HBV DNA at 1-year follow-up.
Six of seven patients with undetectable HDV RNA at the end of 24 weeks of treatment remained HDV RNA negative at 1-year follow-up. The researchers observed that HDV RNA declined more quickly in HBsAg rapid responder patients during REP 2139 exposure compared with those with a slower HBsAg response.
Vaillant told Healio.com/Hepatology that REP 2139 is currently being assessed for safety and tolerability in triple combination therapy with tenofovir and PEG-IFN for 48 weeks. “Information we’ve already shown is that that combination is very well-tolerated and gives a very profound restoration of the immune response,” he said.
Disclosure: Vaillant reports he is an employee and shareholder of Replicor. Please see the full study for the other authors’ relevant financial disclosures.