LYON, France– ENYO Pharma (ENYO), a private clinical stage biotechnology company developing innovative drug candidates, today announced positive proof of concept data from Study EYP001-203 of Vonafexor in combination with pegylated-Interferon (peg-IFN) in viremic patients with chronic hepatitis B (CHB). Vonafexor met the primary endpoint of lowering HBsAg by an average of ≥ 1 log10, a key biomarker of viral activity in the liver, after 16 weeks of treatment. These results in CHB patients are further positive news for Vonafexor, after the recent disclosure of strong positive clinical results in Non-Alcoholic Steato-Hepatitis (NASH) patients on July 28, 2021.
In the EYP001-203 Phase 2a trial, 20 subjects with CHB were randomized 1:1 to receive oral, once-daily Vonafexor at 200 mg in combination with 180 μg peg-IFN subcutaneous injection weekly and also with or without oral once-daily 0.5 mg Entecavir for 16 weeks. The subjects were thereafter maintained for the next 24 weeks on oral, once-daily 0.5 mg Entecavir only.
The study results clearly discriminated between those subjects who were HBeAg negative (n=13) and who significantly responded to Vonafexor plus peg-IFN treatment and those who were HBeAg positive (n=7) who did not respond. Established data on CHB patients confirm that more and more patients are HBeAg negative (>80% currently) as a consequence of the chronic evolution of their disease.
Subjects negative for HBeAg (n=13) had a mean HBV-DNA baseline level of 4.6 log10 IU/mL and a mean HBsAg baseline level of 3.1 log10 IU/mL compared to HBV-DNA level of 7.8 log10 IU/mL and HBsAg level of 4.2 log10 IU/mL for subjects positive for HBeAg (n=7).
In HBeAg negative subjects, HBsAg was reduced by -1 log10 IU/mL compared to baseline after 16 weeks of dual regimen Vonafexor/peg-IFN, while the reduction was only -0.6 log10 IU/mL compared to baseline after triple regimen Vonafexor/peg-IFN/Entecavir. Three out of 13 subjects had a reduction of HBsAg greater than -1 log10 IU/mL after 16 weeks of either dual or triple regimens with 2 out of 13 subjects achieving levels of HBsAg lower than 100 IU/mL.
At week 20 (1 month after stopping the Vonafexor/peg-IFN treatment), 5 out of 12 subjects had a reduction of HBsAg greater than -1 log10 IU/mL with all of these patients achieving levels of HBsAg lower than 100 IU/mL..
In addition, the viremia measured by HBV-DNA decreased rapidly in HBeAg negative subjects to reach levels close to or below the Lower Limit Of Quantification (LLOQ of 20 IU/mL) for both dual and triple regimens.
Vonafexor was safe and well tolerated. Some good Alanine Aminotransferase (ALT) / Aspartate Aminotransferase (AST) flares were observed concomitantly with the decrease of HBV-DNA and HBsAg in 4 out of 10 subjects for the dual regimen combination Vonafexor/peg-IFN and in 8 out of 10 subjects for the triple regimen combination Vonafexor/peg-IFN/Entecavir but these were not associated with an increase of any other liver biomarkers. Mild, transient grade 1 and localized pruritus was observed in some subjects but did not result in discontinuation or withdrawal from the study.
“We were very pleased to obtain these exciting results of Vonafexor in combination with the immune modulator Interferon, in previously untreated and viremic HBeAg negative patients. The results are very encouraging for two reasons: first, the decline seen in HBsAg, reaching an average of -1 log10 is 2 to 3 times greater than what is reported historically with interferon alone, especially in the patients studied who had significant high HBsAg plasma levels at the start of treatment ranging from 340 to 7,050 IU/mL and were therefore a difficult to treat population; And secondly, all subjects had complete viral suppression in less than half of the time needed by usual mono treatment regimens of peg-IFN and/or Nucleot(-s)ides” explained Pietro Scalfaro, MD, ENYO’s Chief Medical Officer.
“In CHB HBeAg negative subjects, Vonafexor combined with peg-IFN induced a rapid, early and significant HBV-DNA decline which translated to its suppression in all 12 subjects after only a few weeks of treatment and 100% of subjects had HBV-DNA levels below LLOQ between weeks 16 and 20. In addition the -1.0 log10 HBsAg reduction seen at week 16 supports further assessment of Vonafexor for its potential to improve functional cure rates with longer treatment duration” commented Prof. Chao-Wei Hsu, MD, Investigator of the trial and Director of Hepatology at Chang Gung Memorial Hospital in Taiwan.
Part of these results were already presented at the recent EASL meeting but more detailed results of this study will be submitted for presentation at a scientific conference in Fall this year.
In the second Phase 2a study reported today (EYP001-201) 26 virally suppressed patients with CHB already receiving chronic daily Nucleot(-s)ides treatment were randomized 2:1 to receive oral, once-daily Vonafexor at 200 mg or Placebo for 16 weeks. The subjects were then maintained for an extra 24 weeks on oral once-daily 0.5 mg Entecavir.
A recent interim analysis conducted by the DSMC (Drug Safety Monitoring Committee) for this study concluded that Vonafexor was well tolerated and safe (no ALT/AST flares were observed) but there was no apparent efficacy benefit of Vonafexor with Entecavir in these virally suppressed CHB patients. Therefore, no additional subjects are being recruited in this trial. These data are somehow consistent with the EYP001-203 study where the triple regimen including Entecavir was apparently less efficacious than the dual regimen without Entecavir.
“These results help us further define the CHB patient population for whom Vonafexor can produce the greatest benefit, namely viremic CHB patients when combined with an immune-modulator as seen in Study 203. We have pre-clinical data to support the synergy of Vonafexor with peg-IFN which suggest that Vonafexor is enabling the innate immune response necessary to help HBeAg negative patients move towards a functional cure” said Pietro Scalfaro, MD, ENYO’s Chief Medical Officer.
“The results of the 203 trial for Vonafexor in combination with Interferon are very encouraging as HBeAg negative patients represent more than 80 % of the CHB patient population. They fully support the continued development of Vonafexor in this population in combination with peg-IFN and we are working on the design of pivotal regulatory studies, including potential combination studies of Vonafexor with therapeutics having other mechanisms of action to maximize the benefit of such treatments for CHB patients.” added Jacky Vonderscher, PhD, co-founder and Chief Executive Officer of ENYO.
