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Spring Bank Announces Positive Results from the Recently Completed Phase 2 Chronic Hepatitis B ACHIEVE Trial and Additional Inarigivir Studies
Consistent reduction in HBV DNA demonstrated with higher inarigivir doses including in high viral burden HBeAg-positive patients
26% HBsAg responder population for all inarigivir doses showed mean HBsAg change of 0.8log10 with a range of 0.5log10 - 1.4log10
Inarigivir 400mg rapidly and uniformly increased activation markers of innate immunity without evidence of tolerance in a new inarigivir study in healthy volunteers
Favorable safety and tolerability profile observed across all doses studied
Conference call to be held today,
In an oral presentation during the General Session II Award Ceremony I at the ILC earlier today, Professor
Across all four dosing cohorts, 16 of the 62 (26%) evaluable patients treated with inarigivir had a 0.5log10 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 0.8log10 with a range of 0.5log10 to 1.4log10. 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. It is important to note that 2 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 significant 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 (82%) 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 (hypertriglyceridemia) was observed, but was not sustained on retesting, and there was one serious adverse event (SAE) 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.
“The data from the ACHIEVE trial demonstrate a clear dose dependent antiviral response on HBV DNA and HBV RNA with inarigivir treatment,” said Professor
Additional inarigivir data announced highlighting immune-activation with the 400mg dose
“The increasing antiviral response seen at the 200mg dose, especially in high viral burden patients, and the clear evidence of innate immune activation at the 400mg dose in healthy volunteers with good tolerability, has led
EASL 2019 ILC Poster Presentation demonstrating antiviral activity of inarigivir in nucleoside- and capsid-resistant HBV variants
In a poster presentation at EASL 2019 ILC, Professor
Professor Locarnini stated, “The sensitivity of both NUC-resistant and CpAM-resistant strains to inarigivir and the lack of cross-resistance is beneficial for combination studies since inarigivir will cover both pre- existing resistant variants and prevent treatment-emergent resistance to both NUCs and CpAM inhibitors,” said Dr. Locarnini.
A replay of the call may be accessed by visiting Spring Bank’s website.
Additional details, including presentation abstracts, can be found on the ILC website at https://ilc-congress.eu/. A copy of the presentation materials can be accessed by visiting the Presentations and Publications section of the
In addition, the forward-looking statements included in this press release represent Spring Bank’s views as of the date hereof.
Source: Spring Bank Pharmaceuticals, Inc.