Clinical Trials
 Arriva is conducting human clinical trials with nebulized, recombinant alpha 1-antitrypsin (rAAT) product to treat hereditary emphysema. The company has completed a Phase 1a safety study and a Phase 1b/2a proof-of-concept study.
Basis for Development
Hereditary Emphysema (HE) is an inherited disorder that results in low- or non-existent levels of alpha 1-antitrypsin (AAT) in the blood. With low levels of AAT the body is less protected from an enzyme in the white blood cells that can cause damage to the air sacs in the lungs. This genetically determined condition may result in serious lung and/or liver disease.
HE has been selected as Arriva's lead indication based on the known efficacy of Prolastin® (plasma-derived AAT). As a treatment for HE, Prolastin® is limited by its availability, expense, and invasive intravenous administration. These factors, coupled with a well-defined patient population, suggest that an approved, inhaled, non-animal sourced AAT product would gain immediate patient acceptance.
Production Capabilities
Arriva scientists have developed several manufacturing systems for large-scale and high-yielding production of stable, non-animal sourced recombinant proteins in yeast. Multi-kilogram quantities of cGMP rAAT have been produced by a contract manufacturer for Arriva’s ongoing clinical development program.
Inhalation Delivery
Arriva's rAAT product is formulated for inhalation delivery into the deep lung, using high-efficiency nebulizers. There, it will effectively bind to and neutralize excess proteolytic enzymes that are responsible for the lung tissue degradation that results in emphysema. Long-term studies with Prolastin® have shown that AAT augmentation therapy safely slows the progression of the disease. Convenient and accessible, inhalation delivery provides patients more immediate control in managing disease symptoms than does the current infusion method.
Exclusive Product Position
Our substantial portfolio of in-licensed and in-house patents for the use of rAAT and other protease inhibitors secures a focused worldwide competitive advantage and provides freedom of operation. The current portfolio includes a number of issued U.S. and European patents. Patent protection continues to grow with additional pending applications filed for novel inventions in the manufacturing and formulation of rAAT.
Arriva has received orphan-drug designation in the U.S. for rAAT for the indications of hereditary emphysema and cystic fibrosis.
Successful Animal Model Studies
In addition to its clinical trial program, Arriva scientists, in collaboration with Harvard University and Washington University, St Louis, have shown that nebulized rAAT was able to reduce significantly the development of emphysema in mice that were exposed to cigarette smoke for a six-month period.
Reference:
P. Pemberton et al., COPD; Journal of Chronic Obstructive Pulmonary Disease, 3:101-108 (2006).
Resources for Patients - Hereditary Emphysema
The Alpha-1Foundation is a national, not-for-profit organization founded in 1995 by three individuals diagnosed with alpha 1-antitrypsin deficiency. The Foundation is committed through its respected members to bringing this genetic disorder into the mainstream of public awareness. The Alpha One Research Network and the Alpha One Registry were founded in 1996 as the centerpieces of the Foundation to establish and promote research studies of alpha 1-antitrypsin deficiency. The Alpha One Registry is a confidential database of individuals diagnosed with alpha 1-antitrypsin deficiency and is the largest national registry of its type in the United States.
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