Spring Bank Pharmaceuticals presents results from ACHIEVE trial at ILC

Spring Bank Pharmaceuticals announced at The International Liver Congress, or ILC, results from the recently completed inarigivir Phase 2 dose escalation ACHIEVE trial for patients with chronic hepatitis B viru, or HBV. Spring Bank is developing inarigivir, an orally-administered hepatic-selective immunomodulator, as a potential backbone in a combinatorial treatment for chronic HBV with the goal to accelerate and substantially increase chronic HBV functional cure rates in a simple, safe and selective manner. In an oral presentation the company presented top-line results from all cohorts including the final 200mg dosing cohort. The data show that inarigivir continued to demonstrate a dose-dependent effect on HBV DNA and HBV RNA in the fourth cohort of the ACHIEVE trial over the 12-week dosing period. Inarigivir 200mg monotherapy dosing exhibited a mean decrease of 1.54log in HBV DNA with a range of 0.71log to 3.26log and a mean decrease of 1.14log in HBV RNA with a range of 0.08log to 4.88log. Inarigivir 200mg monotherapy showed a uniform antiviral response in all patients, in particular the high viral burden HBeAg-positive patients who had not responded to the lower doses of inarigivir monotherapy in the earlier ACHIEVE cohorts. In addition, across all patients HBV DNA and HBV RNA responses correlated with baseline HBsAg, baseline IP-10 and the decline of IP-10 at week 12, comparable to the clinical experience with interferon in chronic HBV. Across all four dosing cohorts, 16 of the 62 evaluable patients treated with inarigivir had a 0.5log or greater reduction in HBsAg at week 12 or week 24 and were categorized as responders. The mean reduction of HBsAg in this responder population was 0.8log with a range of 0.5log to 1.4log. Importantly, the HBsAg response to inarigivir in the ACHIEVE trial was genotype and host dependent. Although the number of patients was small, the HBsAg response seen in Genotype A and D was “excellent” with 4 of 5 patients responding. Genotype B and C were the most common genotypes and 33% of genotype B responded compared to 10% of genotype C. Two of the 3 genotype C patients that responded received 200mg inarigivir dose and belonged to the higher viral burden HBeAg-positive group. This amplified HBsAg response observed with inarigivir in genotype B compared to genotype C is comparable to the clinical experience of the immunomodulator interferon in the treatment of chronic HBV. The overall data from the ACHIEVE trial also revealed evidence of a shutdown of viral transcription by inarigivir in HBeAg-negative patients where HBV RNA was undetectable at week 12 in all patients treated with inarigivir at the 50mg, 100mg, and 200mg doses with a concomitant undetectable HBcrAg in the majority of these patients. At week 24, the HBV RNA and HBcrAg response was sustained with the switch to tenofovir disoproxil fumarate 300mg and associated with 18 of the 22 HBeAg-negative patients also having undetectable HBV DNA. Inarigivir was shown to be well tolerated at all doses in the ACHIEVE trial. Treatment-emergent adverse events ranged from mild to moderate in severity, with no investigator determined interferon-like side effects. The percentage of treatment-emergent adverse effects reported in the ACHIEVE trial was similar between the active and placebo groups. In the fourth cohort, one Grade 3 event was observed, but was not sustained on retesting, and there was one serious adverse event for knee pain hospitalization reported, but this patient was dosed with placebo. There were no other clinical or biochemical events above Grade 3 during the ACHIEVE trial. Spring Bank also announced the results from a healthy volunteer study that examined the potential for the use of the 400mg dose of inarigivir in chronic HBV patients. The results from this study revealed that inarigivir 400mg rapidly and uniformly increased activation markers of innate immunity on circulating peripheral monocytes and dendritic cells which was sustained over a ten-day period of dosing without evidence of tolerance. There was an associated activation of CD8+ t-cells and down-regulation of NK cells resulting in a potentially favorable adaptive immune profile for an antiviral response. The results from this study also demonstrated a lack of systemic cytokine activation secondary to the intra-hepatic targeting of inarigivir resulting in a favorable tolerability profile. These compelling immune-activation data for inarigivir, together with the dose-dependent effects on HBV DNA and HBV RNA and favorable tolerability profile observed up to 200mg daily in the ACHIEVE trial, serve as the basis for the recent launch of the Spring Bank global CATALYST trials in both treatment-naive and virally-suppressed chronic HBV patients. The CATALYST trials will focus on the examination of the 400mg dose of inarigivir.

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