Arrowhead Receives Orphan Drug Designation for ARC-AAT

Home/Newsroom/

Arrowhead Receives Orphan Drug...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical

company developing targeted RNAi therapeutics, today announced the

United States Food and Drug Administration (FDA) has granted ARC-AAT

orphan drug designation. ARC-AAT is Arrowhead’s RNAi-based therapeutic

candidate 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 children

and adults. Arrowhead is currently conducting part B of a Phase 1 study

of ARC-AAT in patients with PiZZ genotype AATD.

“Receiving orphan drug designation is an important milestone in the

development of ARC-AAT, which we think is a very promising program aimed

at providing a better option for patients with liver disease associated

with alpha-1 antitrypsin deficiency,” said Bruce D. Given, M.D.,

Arrowhead’s Chief Operating Officer. “The Orphan Drug Act provides

important incentives for sponsors to develop drugs that treat rare

diseases and we look forward to more engagement with the FDA as the

development of ARC-AAT progresses.”

The ongoing Phase 1 trial of ARC-AAT is a multi-center, randomized,

placebo-controlled, double-blind, single dose-escalation first-in-human

study to evaluate the safety, tolerability and pharmacokinetics of

ARC-AAT and the effect on circulating AAT levels. The study has been

enrolling in dose cohorts of six participants each, with participants

randomized at a ratio of 2:1 (active:placebo) to receive a single

intravenous injection of either ARC-AAT or placebo (normal saline). The

study consists of two parts; Part A in healthy volunteers, which has

been completed, and Part B to be conducted in patients with PiZZ

genotype AATD. The study evaluates participants for 28 days following

dosing, with additional follow-up if needed every 2 weeks until AAT

levels return to baseline.

The FDA Office of Orphan Products Development (OOPD) mission is to

advance the evaluation and development of products that demonstrate

promise for the diagnosis and/or treatment of rare diseases or

conditions. In fulfilling that task, OOPD evaluates scientific and

clinical data submissions from sponsors to identify and designate

products as promising for rare diseases and to further advance

scientific development of such promising medical products. Orphan drug

designation provides incentives for sponsors to develop products for

rare diseases. These incentives include increased engagement with FDA on

drug development activities, exemption from all future product-specific

regulatory fees, the opportunity to apply for R&D funding, tax credits,

an increased chance of priority review, and 7 years of orphan

exclusivity at time of New Drug Application (NDA) approval.

About Alpha-1 Antitrypsin Deficiency (AATD)

AATD is an autosomal recessive genetic disorder associated with liver

disease in children and adults and pulmonary disease in adults. Alpha-1

antitrypsin is a circulating glycoprotein protease inhibitor of the

serpin family encoded by the AAT gene and primarily synthesized in the

liver. The physiologic function is inhibition of neutrophil proteases to

protect healthy tissues during inflammation and prevent tissue damage.

The Z mutant is the most common disease variant and has a single amino

acid substitution that results in improper protein folding causing

severe impairment of secretion from hepatocytes. This lack of secretion

leads to accumulation of mutant Z-AAT polymers, which form globules in

the hepatocyte endoplasmic reticulum. This triggers continuous

hepatocyte injury, leading to fibrosis, cirrhosis, and increased risk of

hepatocellular carcinoma.

In clinical practice, approximately 96-98% of AATD-related disease is

due to the homozygous PiZZ genotype. PiZZ individuals have severe

deficiency of functional AAT leading to pulmonary disease and hepatocyte

injury and liver disease. Lung disease is frequently treated with AAT

augmentation therapy. However, augmentation therapy does nothing to

treat liver disease, and there is no specific therapy for hepatic

manifestations. There is a significant unmet need as liver transplant is

currently the only available treatment for severe liver manifestations.

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 an orphan disease that appears to be

frequently misdiagnosed or undiagnosed. European prevalence is estimated

to be 1 per 2500.

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. ARC-AAT employs a novel unlocked nucleobase analog (UNA)

containing 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.

Reduction of liver production of the inflammatory Z-AAT protein, which

is likely a cause of progressive liver disease in AATD patients, is

important as it is expected to halt the progression of liver disease and

potentially allow fibrotic tissue repair. The Company is conducting a

single dose Phase 1 clinical study, with part A in healthy volunteers

and part B in AATD patients.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing

targeted RNAi therapeutics. The company is leveraging its proprietary

Dynamic Polyconjugate delivery platform to develop targeted drugs based

on the RNA interference mechanism that efficiently silences

disease-causing genes. Arrowhead’s pipeline includes ARC-520 for chronic

hepatitis B virus and ARC-AAT for liver disease associated with Alpha-1

antitrypsin deficiency.

For more information please visit http://www.arrowheadresearch.com,

or follow us on Twitter @ArrowRes.

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

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

Source: Arrowhead Research Corporation

Arrowhead Research Corporation
Vince Anzalone, CFA
626-304-3400
ir@arrowres.com
or
Investor

Relations:
The Trout Group
Todd James
646-378-2926
ir@arrowres.com
or
Media:
Russo

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

Source: Arrowhead Research Corporation

News Provided by Acquire Media