November 15, 2004 02:33 PM US Eastern Timezone
CORRECTING AND REPLACING Dyax and Genzyme Announce Final EDEMA1 Clinical Results at ACAAI Meeting; Positive DX-88 Data for the Treatment of Hereditary Angioedema
Correction...by DYAX BIOWIRE2K
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 15, 2004--Under Header "DX-88 Clinical Trials in HAE", first graph first sentence should read: November 12, 2004 (sted November 12, 2005).
Corrected Release should read:
DYAX AND GENZYME ANNOUNCE FINAL EDEMA1 CLINICAL RESULTS AT ACAAI MEETING; POSITIVE DX-88 DATA FOR THE TREATMENT OF HEREDITARY ANGIOEDEMA
Dyax Corp. (Nasdaq [img]http://uumor.pair.com/nutalle2/peanutallergy/biggrin.gif[/img]YAX) and Genzyme Corporation (Nasdaq:GENZ) today announced final results from their EDEMA1 (Evaluating DX-88's Effects on Mitigating Angioedema) trial, the first successfully completed placebo controlled trial for the treatment of hereditary angioedema (HAE) under a US investigational new drug (IND) application. The EDEMA1 results demonstrate that DX-88 achieved statistical significance with respect to the primary clinical endpoint of the trial; DX-88 was safe and well tolerated; and that DX-88 was effective at treating all types of HAE attacks, including potentially fatal laryngeal attacks. An oral presentation of the final results was made today by Dr. Lynda Schneider, Director of the Allergy Program at Children's Hospital Boston and a lead clinical investigator for DX-88, at the Annual Meeting of the American College of Allergy, Asthma and Immunology (ACAAI).
The EDEMA1 trial was a 48-patient, Phase II, double-blind placebo-controlled, dose escalating clinical trial designed to evaluate the safety and efficacy of Dyax's recombinant small protein DX-88 for the treatment of hereditary angioedema (HAE). HAE is a rare, debilitating and life-threatening acute inflammatory condition characterized by episodes of pain and swelling. There is no approved treatment for HAE in the United States.
With respect to the primary endpoint of the EDEMA1 trial, 72% of patients who were treated with DX-88 (n=40) reported significant improvement of HAE symptoms within four hours of administration, as opposed to a 25% response rate within the placebo group (n=8), a difference of 47% (p=0.0169).
Patients were administered either one of four doses of DX-88 (5, 10, 20 and 40 mg/m2) or a placebo (saline) via a 10-minute intravenous infusion. Response rate was not significantly different between the four dose levels in EDEMA1.
All types of attacks were included in the EDEMA1 trial, including peripheral (46%), abdominal (46%) and laryngeal (8%). Peripheral attacks (hands, feet, face) are the most disfiguring; abdominal attacks are the most painful; and laryngeal attacks can close the airways and are potentially fatal. Across all types of attacks in the trial, the median time to response (onset of significant relief of symptoms) was 70 minutes for the DX-88 group, versus 246 minutes for the placebo group. Patient participants ranged from 10 to 75 years of age.
In EDEMA1 and in all trials to date, including the ongoing EDEMA2 trial in which patients can be treated with DX-88 for up to ten separate HAE attacks, no antibodies to DX-88 have been observed.
"The results from this study are very encouraging and demonstrate the potential of DX-88 to rapidly alleviate the symptoms of HAE attacks," commented Dr. Schneider. "This study represents an important advance in the understanding and management of hereditary angioedema, and I'm very excited to be working with Dyax and Genzyme on our mutual mission to bring forward a treatment for patients who are living today with the uncertainty and fear of the next attack, which could at any time turn fatal."
"We are extremely pleased with the positive EDEMA1 results, and will continue to work with the FDA on defining the shortest route to approval of DX-88 for patients suffering with HAE," stated Henry E. Blair, Chairman, President and CEO of Dyax Corp. "The data presented today provide validation of the positive effect of DX-88 in HAE patients. The results represent a considerable accomplishment for Dyax and Genzyme, and are a testament to the potential benefit of targeted small proteins as novel therapeutics."
Educational Symposium on HAE
Dyax and Genzyme are sponsoring an educational breakfast symposium at the ACAAI meeting at the Hynes Convention Center in Boston on Wednesday, November 17. This symposium will be open to all ACAAI registrants, and will be held in Ballroom B, beginning at 6:30 am and adjourning at 8:00 am. A globally recognized panel of HAE experts will participate in this symposium, titled "Emerging Therapies for Hereditary Angioedema."
DX-88 Clinical Trials in HAE
In the ongoing open label EDEMA2 trial, 60 attacks in 33 patients have been treated as of November 12, 2004. With regard to clinical data accumulated in EDEMA trials to date, over 115 doses of DX-88 have been administered to more than 70 patients. With regard to safety data, over 190 doses of DX-88 have now been administered to more than 120 people.
DX-88 has orphan drug designation in the US and Europe, as well as Fast Track designation in the US for the treatment of HAE.
Hereditary Angioedema (HAE)
HAE is a rare inherited 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. Adult HAE patients often manage the frequency of attacks with the use of anabolic steroids.
In some European countries, there is one marketed product for HAE. This product is plasma derived C1-Inhibitor, which replaces the protein that is missing or dysfunctional in HAE patients. The C1-Inh product, however, carries the potential risk of blood-borne viruses and is a non-specific inhibitor of kallikrein.
DX-88 is a recombinant small protein that inhibits kallikrein in vitro with very high affinity (40 pM Ki) and unlike C1-Inh, does not inhibit any of the other serine proteases against which it was tested. Kallikrein may be the most relevant target in HAE, as it is a key enzyme in the inflammatory cascade, in which it liberates bradykinin, the intermediary of pain and swelling associated with HAE. The compound was discovered at Dyax Corp., and is being developed for the treatment of HAE in a joint venture between Dyax Corp. and Genzyme Corporation.
This press release contains forward-looking statements, including statements regarding the potential use of DX-88 for HAE, the requirements and prospects for regulatory filings for DX-88 and the prospects for small proteins as novel therapeutics. Statements that are not historical facts are based on Dyax's current expectations, beliefs, assumptions, estimates, forecasts and projections about the industry and markets in which Dyax competes. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors which may affect the future use of DX-88 for HAE, the requirements and prospects for regulatory filings for DX-88 and the prospects for small proteins as novel therapeutics include the risks that: DX-88 may not show therapeutic effect or an acceptable safety profile in clinical trials or could take a significantly longer time to gain regulatory approval than Dyax expects or may never gain approval; Dyax is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacture, marketing, sales and distribution of its biopharmaceuticals; DX-88 may not gain market acceptance; Dyax may not be able to obtain and maintain intellectual property protection for DX-88; others may develop technologies or products superior to DX-88 or other small proteins; and other risk factors described or referred to in Dyax's most recent Annual Report on Form 10-K and other periodic reports filed with the Securities and Exchange Commission. Dyax cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Dyax undertakes no obligations to update or revise these statements, except as may be required by law.
Dyax and the Dyax logo are the registered trademarks of Dyax Corp.
EDEMA1 and EDEMA2 are trademarks of Dyax Corp.
This press release contains forward-looking statements, including without limitation statements about: the potential use of DX-88 for HAE; the potential approval of DX-88; plans to continue the clinical development program; and the sufficiency of clinical trial results for obtaining regulatory approval. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the timing of discussions with the FDA and the EMEA regarding clinical studies and approval of DX-88; the timing and content of decisions by the FDA and the EMEA related to clinical trials and approval of DX-88; the actual efficacy and safety of DX-88 for HAE; the actual timing and results of clinical trials; further analysis of clinical trial data; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of the Genzyme Quarterly Report on Form 10-Q for the quarter ended September 30, 2004. Genzyme cautions investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise these statements.