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ARWR: New HBV Clinical Data of ARC-520 Presented at HEP DART Meeting

By Grant Zeng, CFA


The Updated Data 

On December 6, Arrowhead (NASDAQ:ARWR) presented new data of ARC-520 from its Phase II clinical study in patients with chronic hepatitis B virus (HBV) infection at the 22nd biennial HEP DART meeting held in Kona, Hawaii, from Dec. 3-7. ARC-520 is the company’s first-generation RNAi-based clinical candidate. 

In the ARC-520 2001 open label extension study, 8 patients received between 4-9 monthly doses of 4 mg/kg ARC-520 in combination with entecavir.  

The new data demonstrated that 2 of 3 (66.7%) HBeAg positive patients and 2 of 5 (40%) HBeAg negative patients treated with ARC-520 had a sustained host response that persisted after therapy was removed. This host response was characterized by continued reduction of HBV biomarkers such as HBsAg, and was coincided with an uptick in liver enzyme alanine aminotransferase (ALT), which was indicative of host response.  

In the 4 patients that had a sustained host response, the company observed reductions in HBsAg of 5.0, 3.1, 2.4, and 0.6 log10 from baseline, respectively. Following charts show the detailed results for the 4 patients. 


Further, these four patients achieved absolute levels of HBsAg of 58, 2.6, 0.36, and 0.051 IU/ml, respectively. The lowest absolute level of HBsAg was 0.051 IU/ml, below which is considered seroclearance. These patients also achieved reductions in HBV DNA to below the level of quantitation, and deep reductions in core-related antigen (HBcrAg), and HBeAg, with many at or below their respective lower limits of quantitation.

Our Immediate Takeaways 

In this Phase II study of ARC-520, the company has observed in multiple patients continued reductions in key HBV markers long after ARC-520 treatment ceased. This is pretty encouraging in our view. 

We can’t say definitively that this is immune mediated, since we don’t have biopsies or other direct evidence of that, but it’s the first clinical evidence that indicates that an RNAi therapy initiated a favorable host response. This makes us more confident about the company’s next generation RNAi-based candidate ARO-HBV, which may be even more active since it hits both transcripts from cccDNA and integrated DNA.  

Preclinical Data on ARO-HBV

At the HEP DART meeting, Arrowhead also presented select preclinical data on ARO-HBV. Three doses of ARO-HBV in wild type pHBV mice led to reductions in HBV DNA of 3.44 log10 and both HBsAg and HBeAg dropped below the lower limit of quantitation (reductions of greater than 3.0 log10 and greater than 2.2 log10, respectively).

In addition, in a mutated pHBV mouse model that eliminates the HBx trigger site to simulate HBV patients with high levels of integrated HBV DNA relative to cccDNA, a single dose of ARO-HBV led to a reduction in HBsAg of 2.95 log10. The duration of effect was long, with a HBsAg reduction of approximately 2.0 log10 still observed 8 weeks after the dose.


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