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Positive Phase 2 Results Announced for DX-88, Treatment of Hereditary Angioedema
The trial met its primary endpoint, significant improvement in the symptoms of acute attacks of HAE within four hours of treatment, and demonstrated a statistically significant effect of the drug. The safety profile of DX-88 in the trial was similar to placebo. DX-88, a specific and potent kallikrein inhibitor discovered at Dyax, is being developed for the treatment of HAE in a joint venture between Dyax Corp. and Genzyme Corporation.
"We are extremely pleased with these positive results," stated Henry E. Blair, Chairman, President and CEO of Dyax Corp. "The data provides validation of the positive effect of DX-88 in HAE patients. To recognize the promise that DX-88 holds for improving the quality of life of HAE patients is a tremendous feeling. The EDEMA1 results represent a major accomplishment for this program and for Dyax, and are a testament to the power of using targeted small proteins as novel therapeutics."
Dr. Anthony Williams, Senior Vice President of Medical Affairs and Clinical Operations for Dyax added, "We are now continuing patient treatment in our open label repeat dosing EDEMA2 trial, and are also expanding the number of trial sites. To date in human studies involving DX-88, over 140 doses have been administered in over 105 patients. With positive safety and efficacy data in hand, we remain hopeful that the EDEMA1 results, in conjunction with cumulative data from EDEMA2, may be adequate for potential regulatory filings with both the FDA and EMEA. We look forward to further discussions with the agencies to determine remaining requirements to permit those filings."
Richard A. Moscicki, Senior Vice President and Chief Medical Officer for Genzyme, said: "Patients suffering with HAE are desperate for a treatment, and our goal is to make one available to them as quickly as possible. The results from this study are highly encouraging and provide tremendous momentum to this program."
The results released today are topline, and further details regarding results of this trial will be released at the time of presentation of the complete study results at an appropriate scientific meeting and/or publication in a peer reviewed journal.
Hereditary Angioedema (HAE)
DX-88 has orphan drug designation in the United States and Europe for the treatment of HAE, a rare hereditary condition characterized by episodes of acute swelling and inflammation that can peripherally affect the extremities (hands, feet, face), the abdominal tract, the genitalia, and in life-threatening cases, the larynx. The prevalence of hereditary angioedema is believed to be between 1/10,000 and 1/50,000 people worldwide. The condition is caused by a genetic deficiency of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits kallikrein and other serine proteases in the blood.
Abdominal obstruction caused by HAE is often associated with bouts of severe pain, nausea, and vomiting caused by swelling in the intestinal wall. Peripheral attacks are the most physically disfiguring, yet all types of HAE attacks are debilitating. On average, patients have 12 HAE attacks per year which, left untreated, endure for two to five days. The inconsistent nature of HAE attacks contributes to the patients' sense of uncertainty and the fear of having a laryngeal attack that can rapidly close the airways.
Current Treatment of HAE
There is no marketed therapy for HAE in the United States, and adult HAE patients often manage the frequency of attacks with the use of anabolic steroids.
In Europe, there is one marketed product for HAE in some countries. This product is plasma derived C1-Inhibitor, which replaces the missing or dysfunctional protein in HAE patients. The C1-Inh product, however, carries the potential risk of blood-borne viruses and is a non-specific inhibitor of kallikrein.
Kallikrein may be the most relevant target in HAE, as it is the key enzyme in the inflammatory cascade, in which it liberates bradykinin, the intermediary of pain and swelling associated with HAE. DX-88 is a small protein that inhibits kallikrein in vitro with very high affinity (40 pM Ki) and unlike C1-Inh, does not inhibit any other serine proteases against which it was tested.
Source: Dyax and Genzyme