Biotech Values

[DewDiligence]

Researchers Say Drugs for AAT Deficiency Are Useless

[BAX, CSL Behring, TCLR (being acquired by Grifols), and Israel’s Kamada are among the companies that make AAT replacement therapy. Kamada, which recently got approval for its injected AAT, is also working on an inhaled formulation.]

http://www.reuters.com/article/idCNLDE6650DW20100706

›Tue Jul 6, 2010 7:00pm EDT
By Kate Kelland

LONDON, July 7 (Reuters) - Recommendations for expensive treatments made for a genetic disorder called alpha-1 antitrypsin deficiency should be withdrawn because the drugs have no benefit, scientists said on Wednesday.

The disorder causes chronic lung disease and researchers who reviewed data from two trials on 140 patients with it found no evidence that alpha-1 antitrypsin medicines -- made by various drugmakers including Talecris (TLCR), Kamada (KMDA.TA), CSL (CSL.AX) and Baxter (BAX) -- do any good.

Based on this evidence, the researchers said the treatment, which costs up to $150,000 a year in the United States, should not be recommended by doctors and advocacy groups.

"The drug has not shown any clinical benefit, is extremely costly and has important adverse effects," said lead researcher Peter Gotzsche of the Nordic Cochrane Centre at Rigshospitalet in Copenhagen, Denmark.

"In view of the lack of evidence and high cost of treatment, treating alpha-1 antitrypsin deficiency by replacement therapy cannot be recommended."

According to the team, whose work was published in The Cochrane Library journal, recommendations by the American Thoracic Society and European Respiratory Society that promote alpha-1 antitrypsin replacement are "misguided".

"Both societies recommend augmentation therapy for patients with breathing problems related to alfa-1 antitrypsin deficiency. In our opinion, these recommendations are not reasonable," said Gotzsche.

Alpha-1 antitrypsin deficiency affects less than one in 1,600 people. Those who inherit the disorder have low levels of the protein alpha-1 antitrypsin, also called alpha-1 proteinase inhibitor, which protects the tissue of the lungs from destruction by the body's own white blood cells.

At a relatively young age, this can result in symptoms of emphysema, including shortness of breath and wheezing.

The aim of alpha-1 antitrypsin replacement therapy is to give the patient back the protective protein they are missing. This should limit damage to lungs and, ultimately, prevent early death. The protein is usually extracted from blood donated by healthy volunteers [there have also been some programs to make AAT recombinantly].

The researchers reviewed data from two trials involving a total of 140 people with the disorder, all of whom were at a high genetic risk of developing chronic lung disease. In one trial, patients were given intravenous alpha-1 antitrypsin or a placebo every four weeks for three years and in the other, the treatment or a placebo was given weekly for a minimum of two years.

There was no difference between treatment and control groups in terms of exacerbations of lung disease, or quality of life, the researchers found. Combining the results from the trials, Gotzsche's team also found no evidence of a clinically important effect on lung function.

"Indeed the results suggested modest harm, or at best no effect," they wrote in their study. They added that while the treatment might cause a reduction in the deterioration of lung appearance on CT scan, it was "not clear whether this is a clinically meaningful difference."‹