Arrowhead Pharmaceuticals Provides Update on Heparc-2004 Study

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Arrowhead Pharmaceuticals Provides...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) is providing an update on

its Heparc-2004 clinical study of ARC-520, its therapeutic candidate

under clinical investigation for the treatment of chronic hepatitis B

virus (HBV) infection. Heparc-2004 is a multicenter, randomized,

double-blind, placebo-controlled, multi-dose study of ARC-520, which is

currently being performed in up to 12 patients in the United States

under an Investigational New Drug (IND).

Arrowhead was notified today verbally by the United States Food & Drug

Administration (FDA) of its decision to place a clinical hold on

Heparc-2004. The study is on hold while the company provides responses

to questions arising from a nonclinical toxicology study in non-human

primates using EX1, the company’s liver-targeted, intravenously

administered delivery vehicle.

The FDA did not indicate the clinical hold was based on any human

findings. To date, EX1 has been administered over 800 times in more than

300 human study subjects and patients. Across this substantial clinical

experience, only 3 serious adverse events (SAE) have been observed. Two

of these were fevers, treated with acetaminophen, after which the

patients continued on the study with no further complications. The other

SAE was an instance of hepatic carcinoma in a patient with chronic HBV

and cirrhosis, judged by the treating physician to be unrelated to the

drug. A small minority (6%) of infusions in ARC-520 studies have been

associated with infusion reactions, with 4 patients discontinuing

ARC-520 treatment. In addition, across the ARC-520, ARC-521, and ARC-AAT

clinical programs, laboratory values have not been deemed indicative of

any drug-induced organ toxicity.

Arrowhead has not yet received written notice of the clinical hold from

the FDA; however, based on verbal communications the clinical hold was

prompted by deaths at the highest dose of an ongoing non-human primate

toxicology study. This study involves higher doses of EX1 than those

used clinically in humans and higher than those used in the company’s

previous animal toxicology studies. The cause of these animal deaths is

unknown and under investigation. The EX1 delivery vehicle is used in the

company’s ARC-520, ARC-521, and ARC-AAT programs.

Arrowhead remains committed to working collaboratively with regulatory

authorities worldwide. The company has disseminated data from the same

animal study to agencies across our development programs and is

providing updates as appropriate. The company believes the findings in

animal toxicology studies are related to dose level, and that the safety

profile seen in human clinical studies across the three programs

involving EX1 supports continuing all ongoing clinical studies.

About ARC-520

Arrowhead’s ARC-520 is being investigated for its potential to produce

functional cures in patients with chronic hepatitis B virus (HBV)

infection. ARC-520 intervenes upstream of the reverse transcription

process where current standard-of-care nucleotide and nucleoside analogs

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

The small interfering RNAs (siRNAs) in ARC-520 engage the body’s normal

cellular RNAi machinery and direct specific cleavage of HBV RNA

transcripts, thereby reducing the levels of HBV proteins and the RNA

template used to produce viral DNA. Arrowhead is investigating ARC-520

specifically to determine if significantly reducing circulating and

non-circulating viral proteins and RNA will allow for re-constitution of

an effective host immune response and ultimately HBsAg seroclearance,

resulting in functional cure. As many as 350-400 million people

worldwide are chronically infected with the hepatitis B virus, which can

lead to cirrhosis of the liver and is responsible for 80% of primary

liver cancers globally. Arrowhead is currently conducting Phase 2b

multiple dose and combination studies in chronic HBV patients. In

clinical studies to date, the most common reported adverse events in all

subjects completing treatment were upper respiratory infection and

headache.

About ARC-521

Arrowhead’s ARC-521 is being investigated for its potential to produce

functional cures in patients with chronic hepatitis B virus (HBV)

infection. ARC-521 intervenes upstream of the reverse transcription

process where current standard-of-care nucleotide and nucleoside analogs

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

The small interfering RNAs (siRNAs) in ARC-521 engage the body’s normal

cellular RNAi machinery and direct specific cleavage of HBV RNA

transcripts, thereby reducing the levels of HBV proteins and the RNA

template used to produce viral DNA. Designed to complement ARC-520,

ARC-521 is a second-generation HBV candidate that targets HBV mRNA

transcripts from both cccDNA and integrated DNA and is expected to be

most suitable for those patients who tend to have lower levels of viral

cccDNA. Arrowhead is investigating ARC-521 specifically to determine if

significantly reducing circulating and non-circulating viral proteins

and RNA will allow for re-constitution of an effective host immune

response and ultimately HBsAg seroclearance, resulting in functional

cure. As many as 350-400 million people worldwide are chronically

infected with the hepatitis B virus, which can lead to cirrhosis of the

liver and is responsible for 80% of primary liver cancers globally.

Arrowhead is conducting a Phase 1/2 single and multiple dose study in

healthy volunteers and HBV patients.

About ARC-AAT

Arrowhead’s ARC-AAT is being investigated for the treatment of liver

disease associated with alpha-1 antitrypsin deficiency (AATD), a rare

genetic disease that severely damages the liver and lungs of affected

individuals. The mean estimated prevalence of AATD in the U.S. is 1 per

3000-5000, or approximately 100,000 patients. AATD is also an important

cause of pediatric liver disease with an estimated prevalence in

children of approximately 20,000 patients, and 50-80% likely to manifest

liver disease during childhood. It is a rare disease that is frequently

misdiagnosed or undiagnosed. ARC-AAT employs a novel unlocked nucleobase

analog (UNA) containing an RNAi trigger molecule designed for systemic

delivery using the Dynamic Polyconjugate™ delivery system. ARC-AAT is

highly effective at knocking down the alpha-1 antitrypsin (AAT) gene

transcript and reducing the hepatic production of the mutant AAT (Z-AAT)

protein in animal studies. Reduction of liver production of the

inflammatory Z-AAT protein, which is believed to be the cause of

progressive liver disease in AATD patients, is important as it is

expected to halt the progression of liver disease. ARC-AAT was granted

orphan drug designation in both the United States and in Europe, the

latter being held on Arrowhead’s behalf by a local EU representative,

Pharma Gateway AB. Arrowhead is conducting a Phase 1 clinical study of

ARC-AAT, with part A in healthy volunteers (now complete) and part B in

AATD patients, and a Phase 2 multiple dose study in AATD patients.

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. The company’s pipeline includes ARC-520 and ARC-521 for

chronic hepatitis B virus infection, ARC-AAT for liver disease

associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary

angioedema and thromboembolic disorders, ARC-LPA for cardiovascular

disease, and ARC-HIF2 for renal cell carcinoma.

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 the clinical hold of Heparc-2004,

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.

DYNAMIC POLYCONJUGATES is a trademark of Arrowhead

Pharmaceuticals, Inc.

Source: Arrowhead Pharmaceuticals, Inc.

Company contact:
Arrowhead Pharmaceuticals, Inc.
Vince

Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
or
Investor

Relations:
The Trout Group
Chad Rubin
646-378-2947
ir@arrowheadpharma.com
or
Media:
Russo

Partners
Matt Middleman, M.D.
212-845-4272
matt.middleman@russopartnersllc.com

Source: Arrowhead Pharmaceuticals, Inc.

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