Arrowhead Presents New Clinical Data Demonstrating a Sustained Host Response in Hepatitis B Patients Following RNAi Therapy

Home/Newsroom/

Arrowhead Presents New Clinical...

— Up to 5.0 log10 reduction in HBsAg observed; data presented at HEP

DART 2017 —

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) presented new data from

the company’s Phase 2 clinical study in patients that received multiple

doses of ARC-520, the company’s prior generation RNAi-based clinical

candidate against chronic hepatitis B infection (HBV). A maximum

reduction from baseline in HBV surface antigen (HBsAg) of 5.0 log10 was

achieved seven months following the administration of the last dose of

ARC-520, with the lowest absolute level observed being just above the

lower limit of HBsAg quantitation. These data, presented at the 22nd

biennial HEP DART meeting held in Kona, Hawaii, from Dec. 3-7, indicate

that multiple doses of an RNAi-based therapy may lead to a host response

that is sustained after therapy is concluded.

Bruce D. Given, M.D., chief operating officer and head of R&D for

Arrowhead Pharmaceuticals, said: “We believe that achieving a functional

cure of chronic hepatitis B infection will require a sustained host

response, which is likely to be immune mediated. In our Phase 2 study of

ARC-520, multiple patients saw continued reductions in key HBV markers

long after ARC-520 treatment ceased. These data represent the first

clinical evidence that an RNAi-based approach can lead to the type of

favorable sustained host response that we have always believed is

possible. Achieving this result with ARC-520, which was not designed for

activity against HBV s-antigen produced by integrated DNA, provides us

with further confidence that our new RNAi-based compound, ARO-HBV, which

is designed to silence the production of all HBV gene products,

including transcripts derived from integrated DNA, has a good chance of

being a backbone therapy for combinations intended to cure chronic HBV.”

In an oral presentation titled, “Looking Back to Move Forward –

Designing Next Gen RNAi for HBV,” Dr. Given showed key evidence for the

first time that 2 of 3 (66.7%) HBV e-antigen (HBeAg) positive patients

and 2 of 5 (40%) HBeAg negative patients treated with an RNAi-based

therapy achieved a sustained host response off therapy. This was

characterized by continued reduction of multiple HBV viral markers,

including HBsAg, and coinciding with an increase in circulation of liver

enzyme alanine aminotransferase (ALT), indicative of host response. The

new data from Heparc-2001, the company’s Phase 2 open-label extension

study of ARC-520 in combination with entecavir in 8 patients, follows

patients over 7 months after the last ARC-520 dose was administered,

which is the last time point currently available.

In the 4 patients that appeared to have a sustained host response,

observed reductions in HBsAg were 5.0, 3.1, 2.4, and 0.6 log10 from

baseline. In addition, these patients achieved absolute levels of HBsAg

of 58, 2.6, 0.36, and 0.051 IU/ml. The lower limit of quantitation for

this measurement of HBsAg is 0.05 IU/ml, below which would be deemed

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.

Dr. Given also presented select preclinical data on ARO-HBV, a new

therapy for patients with chronic HBV that utilizes the company’s next

generation Targeted RNAi Molecule (TRiM™) platform. Notably, 3 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, Arrowhead created 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. In this model, 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.

ARO-HBV is designed to silence the production of all HBV gene products,

including transcripts derived from integrated DNA, with the goal of

getting to a level where patients’ immune systems can reconstitute,

leading to a sustained host response and ultimately a functional cure.

Arrowhead’s learnings from multiple clinical studies of prior generation

compounds, ARC-520 and ARC-521, and the extensive non-clinical research

completed in multiple species, including long-term treatment of

chimpanzees, have guided the rapid development of ARO-HBV. The results

presented with respect to ARC-520 are not necessarily predictive of

ARO-HBV results.

GLP-toxicology studies are being conducted and Arrowhead is

manufacturing the drug supply necessary to begin clinical studies of

ARO-HBV. The company anticipates filing a Clinical Trial Application by

the second quarter of 2018.

Slides from Dr. Given’s presentation may be accessed on the Events

and Presentations page under the Investors section of the Arrowhead

website.

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable

diseases by silencing the genes that cause them. Using a broad portfolio

of RNA chemistries and efficient modes of delivery, Arrowhead therapies

trigger the RNA interference mechanism to induce rapid, deep, and

durable knockdown of target genes. RNA interference, or RNAi, is a

mechanism present in living cells that inhibits the expression of a

specific gene, thereby affecting the production of a specific protein.

Arrowhead’s RNAi-based therapeutics leverage this natural pathway of

gene silencing.

For more information, please visit www.arrowheadpharma.com,

or follow us on Twitter @ArrowheadPharma.

To be added to the Company’s email list and receive news directly,

please visit http://ir.arrowheadpharma.com/alerts.cfm.

Safe Harbor Statement under the Private Securities Litigation Reform

Act:

This news release contains forward-looking statements within the

meaning of the “safe harbor” provisions of the Private Securities

Litigation Reform Act of 1995. These statements are based upon our

current expectations and speak only as of the date hereof. Our actual

results may differ materially and adversely from those expressed in any

forward-looking statements as a result of various factors and

uncertainties, including the safety and efficacy of our product

candidates, the duration and impact of regulatory delays in our clinical

programs, our ability to finance our operations, the future success of

our scientific studies, our ability to successfully develop drug

candidates, the timing for starting and completing clinical trials,

rapid technological change in our markets, and the enforcement of our

intellectual property rights. Our most recent Annual Report on Form 10-K

and subsequent Quarterly Reports on Form 10-Q discuss some of the

important risk factors that may affect our business, results of

operations and financial condition. We assume no obligation to update or

revise forward-looking statements to reflect new events or circumstances.

Source: Arrowhead Pharmaceuticals, Inc.

Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
or
Investors

and Media:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
britchie@lifesciadvisors.com
www.lifesciadvisors.com

Source: Arrowhead Pharmaceuticals, Inc.

News Provided by Acquire Media