Washington Editor

Israeli biotech Kamada late last week won U.S. approval of Glassia, an alpha-1 proteinase inhibitor, as the first available liquid ready-to-use therapy to treat a rare genetic lung and liver disorder, known as alpha-1-antitrypsin deficiency (AATD).

Shares of the Ness Ziona-based company (TASE:KMDA), which had submitted its biologics license application to the FDA in May 2009 for Glassia, gained 0.99 percent on the Tel Aviv Stock Exchange Tuesday.

Glassia is the fourth alpha-1 proteinase inhibitor to enter the U.S. market for AATD, joining Talecris Biotherapeutic's Prolastin, Baxter Healthcare Corp.'s Aralast and CSL Behring LLC's Zemaira.

All four products are intravenous drugs, which must be infused, either at an infusion center or at home, explained John Walsh, president and CEO of the Alpha-1 Foundation.

Kamada's product adds not only convenience because it does not have to be reconstituted like the other three FDA-approved alpha-1 proteinase inhibitors, but provides another option for patients, he told BioWorld Today.

The alpha-1-antitrypsin protein helps to control neutrophil elastase, an enzyme produced by the body to rid it of damaged cells or bacteria. A lack of alpha-1-antitrypsin leads to damage in the lung tissues.

A deficiency of alpha-1 antitrypsin also can lead to cirrhosis of the liver in infants and children, Walsh noted, adding that AATD affects about 100,000 people in the U.S.

About 5 percent of those AATD patients are infants and children, he said. "We don't know how many present with liver disease as adults," Walsh said. "We are finding more and more adult onset alpha-1-related cirrhosis coming out now that there is more awareness about alpha-1."

Most patients with AATD become symptomatic at about age 35 to 45 years with symptoms of lung disease, typically referred to as alpha-1-related genetic chronic obstructive pulmonary disease, or sometimes called genetic emphysema.

Walsh noted that there is a lack of testing for patients diagnosed with COPD for the alpha-1 gene mutation.

He pointed out that a person's predisposition for the AATD-related COPD depends on exposure to things such as cigarette smoking and workplace elements.

While Walsh said he never smoked nor has he identified any workplace risk exposures, he became symptomatic at age 35, the same age as his fraternal twin brother. Walsh's brother, however, had experienced more childhood lung infections, had some cigarette and workplace exposure and currently is on full-time supplemental oxygen and on the lung transplant list.

Walsh, on the other hand, still has 30 percent of normal lung function and only has to use oxygen when he takes airline flights or exercises, he said.

He noted he and his brother are 61 years old, which is seven years past the life-expectancy for AATD, based on results of the only definitive longitudinal disease progression study, which was conducted in the late 1980s to mid-1990s by the National Heart, Lung and Blood Institute.

The study was a Phase IV requirement by the FDA for Prolastin, Walsh said.

The alpha-1 gene mutation was initially identified nearly three decades ago by researchers at the National Institutes of Health, he noted.

Shortly after that, Bayer Healthcare picked up development of Prolastin to treat AATD. The company sold the drug to Talecris in 2005. But, Walsh emphasized, had it not been for the Orphan Drug Act of 1983, that product and those that followed may have never been commercialized.

"This was the perfect example of the essence of the Orphan Drug Act, where you have discovery for a potential therapeutic at the NIH literally in the lab, and it was commercialized because of the Orphan Drug Act and made available to patients," he said.

People with alpha-1 deficiency are born with two defective alpha-1 antitrypsin genes, one from each parent, Walsh said.

With four alpha-1 proteinase inhibitors now approved, he said patients are awaiting the approval and availability of an inhaled version of the products, which Walsh said would be a more fast-acting drug and more convenient for patients.

Walsh noted that Talecris and Kamada both are developing inhaled formulations.

"We are committed to the alpha-1 patient community and take great pride in further developments of our second-generation product," Kamada CEO David Tsur said in a statement.

The potential for an aerosolized alpha-1 proteinase inhibitor also could be a therapeutic for patients with cystic fibrosis and nongenetic-related emphysema, Walsh said.