HAE Clinical Trials Offer Hope for Better Therapeutic Alternatives

Five companies are currently conducting HAE clinical trials. Below we summarize the status of each company's clinical program.

LEV PHARMACEUTICALS-C1 INHIBITOR CONCENTRATE (double nanofiltered)

On March 14, 2007, Lev Pharmaceuticals announced positive results in a phase 3 pivotal trial that tested the effectiveness and safety of the Company's C1 inhibitor concentrate product. The trial involved 71 patients who were treated at 20 US medical centers. The European brand of this product has an impressive safety record spanning three decades; and the version that will be sold in the US offers enhanced assurance by adding double nano filtration.

The Lev Pharma trial validated C1 inhibitor's usefulness for treating acute HAE attacks by exceeding the benchmark statistic FDA and others use to assess effectiveness. The company expects to submit an application for obtaining FDA approval within the next couple of months. FDA has agreed to expedite its review of Lev Pharma's licensing application, so it is conceivable that we will have an approved C1 inhibitor product available by the end of the year.

Lev Pharma is also examining the effectiveness of C1 inhibitor in preventing the frequent attacks experienced by more severely affected HAE patients. This study involves scheduled twice weekly infusions, and is expected to conclude in the second half of 2007.

JERINI AG-B2 BRADYKININ RECEPTOR ANTAGONIST

The German biotechnology company Jerini AG has completed a US clinical trial of their B2 bradykinin receptor antagonist--Icatibant. Jerini reported that although the results of this trial were clinically relevant, the focus of the study--median time to onset of symptom relief of drug versus that of placebo--did not reach statistical significance. A separate concurrent study conducted mostly in Europe did show a statistically significant difference between Icatibant and Tranexamic Acid (which is used as an acute therapy by some European doctors). In a February 27, 2007 press release, Jerini announced that it plans to submit a New Drug Application (NDA) to the FDA in the third quarter 2007.

DYAX CORP-KALLIKREIN INHIBITOR

In April of 2007, Dyax announced that it achieved statistically significant results in its phase 3, 72-patient, placebo-controlled, multi-center trial that tested the efficacy and safety of its drug-Ecallantide-to treat patients suffering from moderate to severe HAE attacks. The company reported that the drug was well tolerated and their were no drug related serious adverse events. Ecallantide is a recombinant kallikrein inhibitor that is administered via subcutaneous injection.

In April, Dyax also announced that it had begun another confirmatory placebo-controlled trial that the FDA requested to further validate the patient reported outcome instrument used for demonstrating efficacy in the phase 3 trial. The company projects FDA approval in 2008.

PHARMING NV-Recombinant C1 INHIBITOR

The Dutch biotechnology company, Pharming NV is testing their recombinant C1 inhibitor product in the US. Pharming's product is derived from the milk of female rabbits that have been genetically altered to produce the human C1 inhibitor protein. The drug has been tested in European HAE patients, and preliminary results from non placebo controlled studies indicate treatment outcomes similar to what is observed in patients treated with plasma derived C1 inhibitor concentrate. Patient recruitment for Pharming's Phase 2 US trail is ongoing.

ZLB BEHRING--name recently changed to--CSL BEHRING-C1 INHIBITOR CONCENTRATE

CSL Behring is conducting a Phase III pivotal study of Berinert-P, a C1 inhibitor concentrate product that is produced from US source plasma at the company's plant in Marburg, Germany, and sold throughout the world. Berinert-P has an impressive long term safety record and, in countries where available, is the drug of choice for acute HAE attacks. Several dozen US HAE patients have been purchasing Berinert-P under the auspices of the FDA's Personal Importation Guideline for over three years. Patient recruitment is ongoing.