Status: BLA approved in 2010; also marketed in various countries internationally

Organizations involved:

Kamada Ltd. – Manuf.; R&D; Tech.; Intl. mark.

Baxter Hyland Immuno – USA mark.

Baxter Healthcare Corp. – Parent

Cross ref.: See the entries for Antitrypsin, alpha-1 Products and other specific antitrypsin, alpha-1 products.

Description: Glassia is a high purity aqueous formualtion of Plasma-derived alpha-1-proteinase Inhibitor (Human) for intravenous administration with manufacture including two viral inactivation/removal processes -- solvent-detergent viral inactivation and nanofiltration. Glassia is prepared from human plasma obtained from US.-licensed plasma collection centers by a modified version of the cold ethanol fractionation process and the Alpha1-PI is then purified using chromatographic methods. Kamada reports, "This AAT product is the only available product presented in a stable, ready-to-use liquid form. In addition to its high safety profile, it is also stabilizer free and one of the purest products at present on the market...The product is produced using a sophisticated, chromatographic purification method." The major difference between GLASSIA and other licensed Alpha1-PI products is that GLASSIA is a liquid product while all other licensed products are lyophilized.

Single use vials each contain 1 gram of functional Alpha1-PI in 50 mL of ready to use solution for intravenous injection. Glassia is packaged in 50 mL vials containing 2% solution of active AAT in phosphate-buffered saline. In various countries, it has a dating period of 2 years at 2-8˚C (refrigerated). In the U.S., the dating period is 24 months from the date of manufacture when stored at 2-8ºC, with the date of manufacture defined as the date of final sterile filtration of the formulated drug product. Following the final sterile filtration, no reprocessing/reworking is allowed without prior approval from FDA. GLASSIA contains no preservatives and no latex. No animal-derived (i.e., non-human) source materials or reagents are used in the manufacture of GLASSIA.

Glassia is subject to FDA lot release inspection requirements.

Nomenclature: Antitrypsin, alpha-1/Kamada [BIO]; Glassia [TR US]; Respira [TR internationally]; alpha-1-Proteinase Inhibitor (Human) [FDA USAN INN]; A1P1 [SY]; AAT [SY]; alpha-1 antitrypsin [SY]; Intravenous AAT [SY]; IV-AAT [SY]

Companies.: Glassia is marketed by Baxter Hyland Immuno in the U.S. Kamada has established a network of marketing partnerships with distributors worldwide. In Aug. 2010, Kamada granted Baxter rights in the U.S., Australia, New Zealand and Canada. The distribution agreement includes an upfront cash payment by Baxter of $20 million.

Manufacture: Plasma processing includes proprietary protein purification technology for manufacture high quality product at high purity levels. The product undergoes double viral elimination/inactivation.

Individual plasma units used for production of GLASSIA are tested using FDA-licensed serological assays for hepatitis B surface antigen (HBsAg) and for antibodies to hepatitis C virus (HCV) and HIV types 1 and 2 (HIV-1/2), as well as by FDA-licensed Nucleic Acid Testing (NAT) for HCV and HIV-1. Each plasma unit must be non-reactive (negative) in all tests. Plasma is also tested by in-process NAT procedures for parvovirus B19 and the limit for B19 DNA in the manufacturing pool is set not to exceed 10.sup.4 IU per mL. To reduce the risk of viral transmission, the manufacturing process for GLASSIA includes two steps specifically designed to remove or inactivate viruses. The first is nanofiltration (NF) through a 15 nm filter which can remove both enveloped and non–enveloped viral agents and the second is solvent/detergent (S/D) treatment with a mixture of tri-(n-butyl) phosphate (TNBP) and polysorbate 80 (Tween 80) which inactivates enveloped viral agents such as HIV, HBV and HCV. FDA class: Biologic BLA Approvals: Date = 20100709; full BLA (STN 125325/0) Indication = emphysema Indications: [Full text of the INDICATIONS AND USAGE" section of the product insert/labeling]:
GLASSIA is an alpha1-proteinase inhibitor that is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha1-proteinase inhibitor (Alpha1-PI), also known as alpha1-antitrypsin deficiency.
The effect of augmentation therapy with any alpha1-proteinase inhibitor on pulmonary exacerbations and on the progression of emphysema in lpha1-PI deficiency has not been demonstrated in randomized, controlled clinical trials.
Clinical data demonstrating the long-term effects of chronic augmentation and maintenance therapy of individuals with GLASSIA are not available.
GLASSIA is not indicated as therapy for lung disease in patients in whom severe Alpha1-PI deficiency has not been established.
Status: The product is approved in some countries, presumably including some individual European countries (not the EU), and is used under "compassionate use" programs in some countries.

On June 1, 2009, Kamada filed a BLA for FDA approval of Intravenous AAT for chronic replacement therapy in individuals with congenital Alpha-1 Antitrypsin deficiency with demonstrable panacinar emphysema. The BLA received standard priority, i.e., 10 months PDUFA date, an the review cycle was extended by 3 months due to a major amendment received on March 11, 2010.

On July 10, 2010, FDA approved Glassia. Glassia is subject to CBER lot release requirements. CBER does not perform routine lot-release testing for the licensed lyophilized Alpha1-PI products as lot-release tests performed by the manufacturers appear to be appropriate to assure their safety and potency. However, due to concerns "that in GLASSIA, small numbers of particulates appear to be fairly common (from FDA SBA)," CBER requires lot release inspection.

Kamada had originally filed with FDA for use of "Apikam" as the U.S. trade name, but this was denied.

On Oct. 25, 2010, Baxter launched Glassia in the U.S., with it being the first available ready-to-use liquid alpha1-proteinase inhibitor.

As with other AAT products, "The effect of augmentation therapy with GLASSIA or any Alpha1-PI product on pulmonary exacerbations and on the progression of emphysema in Alpha1-PI deficiency has not been demonstrated in randomized, controlled clinical trials. Clinical data demonstrating the long term effects of chronic augmentation and maintenance therapy of individuals with GLASSIA are not available. GLASSIA is not indicated as therapy for lung disease in patients in whom severe Alpha1-PI deficiency has not been established." Medical: The recommended dose is 60 mg/kg body weight once weekly. Marketing: In addition to marketing biological therapeutics for the disorder, Baxter is also working to improve awareness and early diagnosis of AAT deficiency. Baxter sponsors the AlphaTest kit to make it easy for physicians to test patients through a simple finger stick. To date, Baxter has helped screen more than 85,000 people for AAT deficiency. Ongoing: Kamada is developing an aerosolized AAT treatment in collaboration with PARI, a German manufacturer of inhalation devices.