Dyax Announces Results from Two Clinical Trials of DX-88
Thursday June 30, 7:30 am ET
Trials to Proceed with Subcutaneous Dosing of DX-88 for the Treatment of Hereditary Angioedema
CAMBRIDGE, Mass.--(BUSINESS WIRE)--June 30, 2005--Dyax Corp. (Nasdaq:DYAX - News) today announced positive topline results from its completed Phase I trial to evaluate safety and pharmacokinetics (PK) of subcutaneously administered DX-88 in normal volunteers. The Company also announced the presentation today at the World Allergy Congress in Munich of positive interim results from the first 120 attacks of hereditary angioedema (HAE) treated with intravenously administered DX-88 in its open-label, repeat dosing Phase II trial referred to as EDEMA2. DX-88 is being developed in a joint venture with Genzyme Corporation for the treatment of HAE, a debilitating and life-threatening inflammatory condition characterized by unpredictable attacks of severe peripheral, abdominal and/or laryngeal pain and swelling.
Based on the pharmacokinetic and safety profiles observed in the Phase I trial, Dyax has begun to convert HAE patients in the ongoing EDEMA2 trial from intravenous (IV) dosing to the more easily administered subcutaneous (SQ) version of DX-88. The corresponding amendment to the EDEMA2 study protocol has been cleared by the United States Food and Drug Administration (FDA) and Health Canada, and Dyax has begun to receive Investigational Review Board (IRB) approvals necessary to implement the conversion to SQ dosing of DX-88 at 24 active trial sites. This conversion will allow for patient experience with SQ DX-88 prior to the initiation of a pivotal Phase III trial planned for later this year. The data analyzed to date clearly support the program objective to shift from IV to SQ administration of DX-88 in HAE patients.
Dyax and Genzyme are committed to being first to market in the US and EU with a recombinant, non-plasma derived, subcutaneously administered product for HAE that will maximize patient convenience and market potential. Currently in the US, there is no marketed therapeutic for acute attacks of HAE. Dyax expects to begin filing a Biologics License Application (BLA) for DX-88 in HAE in 2006, and plan for regulatory approvals in the US and EU during 2007.
Phase I Topline Results
The Phase I trial, performed in 17 normal volunteers, was designed to compare the relative bioavailability of intravenous (IV) and subcutaneous (SQ) administration of 10 mg and 30 mg doses of DX-88. Other pharmacokinetic (PK) parameters were also assessed, in addition to general safety and tolerability. Topline analysis revealed that bioavailability was equivalent for SQ and IV administered doses. Other PK parameters were as predicted for SQ DX-88 relative to IV, including reduced peak blood levels and prolonged duration of pharmacologically active concentrations of DX-88 (depot effect). The overall safety profile was favorable for both routes of administration. Specifically, the SQ route was well tolerated with regard to local site reactions.
EDEMA2 Interim Results
EDEMA2 is a dose-ranging, open-label, repeat dosing study designed to evaluate the safety and clinical effect of DX-88 when administered multiple times to individual patients for separate HAE attacks. Clinical results undergo a planned analysis after every 60 attacks treated in this ongoing trial.
As presented today at the World Allergy Congress by Dr. Timothy Craig, DO, Professor of Medicine and Pediatrics at Penn State University and an investigator for the EDEMA2 trial, the interim data support that DX-88 can provide substantial therapeutic benefit to HAE patients, with no apparent decrease in drug effect in patients exposed to multiple doses. In the analysis, 120 HAE attacks were observed in 47 patients treated with IV DX-88. The results confirm earlier analysis indicating that the drug is well tolerated and can rapidly relieve HAE symptoms irrespective of the number of and/or type of attack, and regardless of patient demographics. The median age of patients treated in the trial was 31 years, ranging from 11 to 78 years of age.
Today's presentation of data also reaffirm earlier observations of high initial response rates across all three dose levels used in the trial. The median time to clinical response, defined as onset of relief of HAE symptoms within four hours post-dosing, was 30 minutes. Left untreated, HAE attacks last for an average of two to five days.
Initial response rates at each dose level were: 92% at 5 mg/m(2) (n=24), 89% at 10 mg/m(2) (n=81) and 100% at 20 mg/m(2) (n=15). The data to date indicate a more durable, sustained response, as measured by the percentage of patients who received a subsequent dose for a single attack, at the two highest dose levels of 20 mg/m(2) (0%, n=15) and 10 mg/m(2) (12%, n=81), as compared to the lowest dose level of 5 mg/m(2) (25%, n=24). Based on this durability of response data, patients in the trial will be converted from the current 10 mg/m(2) intravenous DX-88 dose (on average, equivalent to a flat 19 mg dose) to a flat 30 mg dose of subcutaneously administered drug as IRB approvals are received.
All types of HAE attacks were included in the interim EDEMA2 analysis: peripheral (42%); abdominal (46%); and laryngeal (12%). To date, there has been no substantial difference in response rates by attack location. The successful treatment of laryngeal attacks is especially critical, as this potentially fatal type of attack can cause airway blockage requiring emergency intubation.
With respect to repeat dosing with DX-88 for separate HAE attacks, twelve patients in the analysis were treated multiple times with no decrease in drug effect observed. The Company continues to screen for development of antibodies to DX-88, and to date, none have been detected.
All patients in the interim analysis received DX-88 by intravenous infusion over a ten-minute period. Dosing is currently followed by a four hour physician observation period. No drug-related serious adverse events have been reported in EDEMA2, contributing to the overall benign safety profile for DX-88.
Commenting on today's announcements, Thomas R. Beck, Executive Vice President, Business and Product Development for Dyax commented, "I am greatly encouraged by both sets of results announced today. These data, and the conversion to subcutaneous DX-88 in our open-label EDEMA2 trial, are setting a clear course for initiation of our pivotal Phase III trial. We expect that moving to a 30 mg fixed dose, in combination with the depot effect observed with SQ DX-88, should preserve high initial response rates while maintaining a highly durable, sustained response. Given the level of physician and patient demand for a convenient product that can ultimately be self-administered at the onset of an HAE attack, I expect rapid enrollment into the EDEMA3 trial and continued growth in the already large number of DX-88 trial sites. Thanks to the HAE patient and medical community, the volume and scope of data being collected in the EDEMA trials are unparalleled in this indication and should help to secure the path toward approval of DX-88 for HAE."
DX-88 Trials and Cumulative Data
Dyax has successfully completed two Phase II trials, EDEMA0 and EDEMA1, of DX-88 for the treatment of HAE. A third Phase II trial, EDEMA2, is ongoing.
EDEMA0 was a 9-patient, open-label, single dose, dose ranging trial conducted in the EU. All patients responded.
EDEMA1 was a 48-patient, double-blind placebo-controlled, single treatment, dose ranging trial conducted in the US that demonstrated statistically significant clinical response (p=0.0169) for patients receiving DX-88 (72% response, n=40) versus patients receiving placebo (25% response, n=8), as measured by significant improvement in HAE symptoms at four hours post-dosing. In EDEMA1, DX-88 was well tolerated and provided clinical benefit for all types of HAE attacks, including potentially fatal laryngeal attacks.
The most recent results from the ongoing EDEMA2 trial are reported above, and are consistent with the potential of DX-88 to safely and repeatedly provide substantial therapeutic benefit to patients with acute attacks of HAE, irrespective of patient gender, age, or clinical presentation.
With regard to clinical data accumulated in EDEMA trials to date, over 235 doses of DX-88 have been administered to over 95 patients. With regard to safety data, over 365 doses of DX-88 have now been administered to over 165 people.
DX-88 for use in treating HAE has orphan drug designation in the United States and Europe, and Fast Track designation in the United States. ... |
