Talecris Biotherapeutics presented results last week from two phase III studies assessing the safety, tolerability and pharmacokinetic comparability of a more concentrated formulation of Prolastin® (Alpha1-Proteinase Inhibitor [Human]) produced via a modification of the current manufacturing process that incorporates technological changes.

Prolastin is indicated for the treatment of alpha1-antitrypsin (AAT) deficiency, a genetic condition in which low levels of the essential blood protein alpha1-proteinase inhibitor (A1PI) can cause emphysema. The more concentrated formulation of Prolastin delivers the same quantity of protein within a smaller infusion volume, potentially cutting infusion time in half for most patients.

Data from these phase III studies presented at the annual meeting of the American Thoracic Society show that the more concentrated formulation of Prolastin had comparable pharmacokinetic and safety profiles to the currently marketed version of Prolastin.

“The significant investment made to incorporate technological changes into our manufacturing process illustrates our long-term commitment to advancing the care of the global alpha-1 patient population,” said Steve Petteway, Ph.D., Senior Vice President, Research and Development for Talecris.

Submissions for approval of the more concentrated formulation of Prolastin have been made in the United States and Canada to the respective regulatory agencies. A similar submission is planned for Europe.

Study Design and Results

Pharmacokinetic (PK) study

Twenty-four subjects were enrolled in a 24-week, multicenter, randomized, double-blind crossover trial that also included an open-label treatment phase with the more concentrated formulation of Prolastin only. The primary endpoint of the study was a measure of drug absorption over time, known as area under the concentration time curve (AUC), measured over the first seven days. Study results demonstrated the following:

- Prolastin and the more concentrated formulation of the product have comparable AUC measures with a 90 percent confidence interval (geometric LS mean ratio = 1.03)

- Four additional PK measures (Cmax, Tmax, T ½ and mean Ctrough) provided further support that the PK profiles of the more concentrated formulation and currently marketed version of Prolastin are essentially superimposable

- Adverse events (AEs) were reported at rates of 0.117 and 0.078 per infusion for the more concentrated formulation and the currently marketed version of Prolastin, respectively, with comparable severity of AEs between treatments

Safety and Tolerability Study

Thirty-eight subjects, 19 of whom were naïve to A1PI therapy, were enrolled in a multicenter, open- label trial in which they received weekly intravenous infusions of the more concentrated formulation of Prolastin dosed at 60 mg/kg. The study was designed to assess the safety and tolerability of the more concentrated formulation of Prolastin over 20 weeks and to describe the nature and frequency of drug-related adverse events. Among the results:

- The more concentrated version of Prolastin was generally well tolerated in naïve and treatment-experienced adult subjects with AAT deficiency

- The adverse event profile of the more concentrated formulation of Prolastin was consistent with the known adverse event profile of the currently marketed version of the product, according to the study

The most common drug-related adverse reactions observed at a rate of ?1.6% in subjects receiving the more concentrated version of Prolastin were chills, malaise, headache, rash, hot flush and pruritus. During clinical studies one patient withdrew from the trial due to a recurrent rash.

About Prolastin®

Prolastin is derived from human plasma and is administered intravenously to raise the levels of AAT in the blood and lungs. Prolastin, Alpha1-Proteinase Inhibitor (Human), is indicated for chronic augmentation and maintenance therapy of individuals having congenital deficiency of alpha1 PI (alpha1 antitrypsin deficiency) with clinically demonstrable panacinar emphysema. Prolastin was the first plasma-derived AAT augmentation therapy to receive approval from the U.S. Food and Drug Administration (FDA) and was approved in December 1987 and launched in February 1988.

Important Safety Information

In clinical studies with Prolastin, reactions were observed in 1.16% of infusions, the most common events being fever (0.77%), light-headedness (0.19%) and dizziness (0.19%). Prolastin is made from human plasma. As with all plasma-derived therapeutics, the potential to transmit infectious agents, such as viruses and, theoretically, the Creutzfeldt-Jakob (CJD) agent that can cause disease, cannot be totally eliminated. There is also the possibility that unknown infectious agents may be present in such products. Individuals with selective IgA deficiencies who have known antibody against IgA (anti-IgA antibody) should not receive Prolastin, since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present. For additional information on Prolastin, please see full prescribing information at http://www.prolastin.com.

About Alpha1-Antitrypsin Deficiency

Alpha1-antitrypsin deficiency, also known as AAT deficiency or alpha-1, is an inherited disorder that causes significant reduction in the naturally occurring protein AAT. It is most common in the Caucasian population of northern Europe and North America. AAT deficiency is also the most common cause of genetic liver disease in children, and genetic emphysema (shortness of breath) in adults. Individuals with AAT deficiency often develop severe obstructive pulmonary disease (COPD) causing disability and premature death. AAT deficiency is estimated to affect 150,000 people in North America and Europe.

Source
Talecris Biotherapeutics

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