Spring Bank has positive Phase 2, expands hep B trial with Gilead

Spring Bank Pharmaceuticals (SBPH) announced positive results from the third cohort (inarigivir 100mg) of Part A of the ongoing Phase 2 ACHIEVE trial. Spring Bank also announced the expansion of the Phase 2 clinical trial being undertaken by Gilead Sciences (GILD) to include up to two additional cohorts of inarigivir co-administered with tenofovir alafenamide 25mg in chronic hepatitis B patients. Spring Bank is developing inarigivir, an orally-administered investigational selective immunomodulator, as a potential backbone in a combinatorial treatment for chronic hepatitis B virus, with a goal to accelerate and substantially increase functional cure rates in a simple, safe and selective manner. Spring Bank has already randomized the majority of the patients in the fourth and final cohort (inarigivir 200mg) of the ACHIEVE trial and anticipates that it will have top-line results by the end of 2018. In the third cohort, 20 patients were randomized; 17 on inarigivir 100mg (13 HBeAg-positive, 4 HBeAg-negative) and 3 on placebo. The primary endpoints, safety and antiviral activity, were achieved at both week 12 (inarigivir monotherapy) and week 24 (following the switch to tenofovir disoproxil fumarate 300mg after week 12). Inarigivir was well-tolerated with no serious adverse events observed. Overall, treatment-emergent adverse events ranged from mild to moderate in severity, with no observed interferon-like side effects or clinical or biochemical events above Grade 3. One HBeAg-negative patient on inarigivir alone had an ALT flare greater than200 IU with reductions in HBV DNA and HBsAg consistent with previously described inarigivir immune flares. Overall, mean HBV DNA reduction at week 12 was 1.0log10, with a mean 0.55log10 reduction in HBeAg-positive patients and a mean 2.26log10 reduction in HBeAg-negative patients, which was significantly superior (t-test: p=0.006) to combined placebo from all groups (n=11). Similar log reductions were seen for the secondary endpoint of HBV RNA reduction, with a mean 0.6log10 reduction in HBeAg-positive patients and a mean 1.4log10 reduction in HBeAg-negative patients. Three patients had a greater than 0.5log10 reduction in HBsAg at either week 12 or week 24. Overall, 13 of 47 (28%) of inarigivir-treated patients in the ACHIEVE trial have had a predefined HBsAg response of 0.5log10 decrease, with a mean decrease in the responder group of 0.8log10 (range 0.5 – 1.4log10) at either week 12 or week 24 after the switch to TDF. Baseline HBsAg level less than 10,000 IU (4log10) remains the strongest predictor of response to inarigivir across all cohorts for HBV DNA and HBV RNA reductions irrespective of HBeAg status. This response is consistent with the known role of HBsAg as a down regulator of the host immune response to HBV. Detailed results from this third cohort will be presented at a future medical conference

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