HEREDITARY ANGIOEDEMA  

DYAX’ DX-88

 We love to see new drugs treat diseases that have yet to find specific treatments. One of the treatments that are are promising is Dyax’ (DYAX) DX-88 (ecallantide) for the treatment of hereditary angioedema (HAE).

 Why important?

Because the attacks can be life-threatening if laryngeal edema occurs and obstructs patients airways. Acute swelling and inflammation can peripherally affect the extremities (hands, feet, face). When they occur, peripheral attacks are the most physically disfiguring. All types of HAE attacks are debilitating. Severe facial edema can also progress to the larynx. Abdominal obstruction caused by HAE is often associated with bouts of severe pain, nausea, and vomiting caused by swelling in the intestinal wall.

On average, patients have 12 HAE attacks per year which, if 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.

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. There is no marketed therapy for acute attacks of HAE in the United States. Adult HAE patients often manage the frequency of attacks with the long-term use of steroids.

In some European countries, plasma derived C1-Inhibitor is available. However, as with all plasma based products, C1-INH carries the potential risk of blood-borne viruses and is also a non-specific inhibitor of kallikrein.

Dyax’ DX-88

DX-88, was discovered at Dyax and is being developed in a joint venture with Genzyme GENZ), is the most advanced investigational drug in the U.S. for the treatment of acute attacks of HAE. The drug 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. 

 In a presentation at the 4th European C1-INH Deficiency Workshop that will be held in Budapest, Hungary from April 29 through May 1, 2005 Dyax intends a to highlight collective results from the its clinical trials of DX-88 (ecallantide) for the treatment of hereditary angioedema (HAE). The presentations will feature positive results from three Phase II trials that demonstrate DX-88's tolerability and ability to elicit rapid and durable clinical responses in HAE patients.

Dr. Marco Cicardi, M.D., a well-known expert in the clinical management of patients with HAE, will present on the topic of "DX-88 Clinical Experience Across EDEMA Trials by Location of HAE Attack." The findings demonstrate that all types of HAE attacks can be successfully treated with DX-88. Notably, life-threatening laryngeal attacks of HAE have responded particularly well; 94% of 18 laryngeal attacks analyzed to date experienced onset of symptom relief in a median response time of 27 minutes post-dosing with DX-88.

Dr. Bruce Zuraw, M.D. will present "A Multicenter, Double-Blind Placebo-Controlled Study of DX-88 in Hereditary Angioedema: Final results from this trial showed a statistically significant benefit for patients treated with DX-88 versus placebo; 72% of patients treated with DX-88 (n=40) reported significant improvement of HAE symptoms within four hours of administration, as opposed to 25% of patients within the placebo group (n=8), a difference of 47% (p=0.0169). 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 as compared to 246 minutes for the placebo group. Patient participants ranged from 10 to 75 years of age.

Dr. Timothy Craig, D.O. will present "A Multicenter, Open Label, Repeat Dosing of DX-88 in HAE: Interim Results of the EDEMA2 Study." EDEMA2 is an ongoing, open label, Phase II repeat dosing study to evaluate the safety and efficacy of DX-88 when administered to patients multiple times for separate HAE attacks. Interim results based on the first 61 attacks treated highlight that DX-88 is well tolerated and can elicit rapid clinical responses, with a median time to initial response (onset of relief of symptoms) of 35 minutes. DX-88 has also retained its clinical effect on repeat treatment for separate HAE attacks. The maximum number of attacks treated to date in any one patient is 14, and this patient continues to respond well. To date, 133 HAE attacks have been treated in 49 patients at 24 active EDEMA2 trial sites.

To date, Dyax has successfully completed two Phase II trials (EDEMA0 and EDEMA1), and is conducting one active Phase II trial (EDEMA2) of DX-88 in HAE. In these trials, over 185 doses of DX-88 have been administered to over 85 HAE patients by a 10-minute IV infusion.

Based on positive animal study results, DYAX has recently begun a Phase I safety and pharmacokinetics study using a subcutaneous formulation of DX-88 in human volunteers. Data from this trial is expected to support the Company's plans to conduct its pivotal Phase III trial using this easily administered formulation.

DX-88 for the treatment of HAE has orphan drug designation in the U.S. and Europe, as well as Fast Track designation in the U.S.

Comments: Read upcoming Prohost Newsletter.  

EBOLA VACCINE

CRUCELL N.V. (CRXL)

 New results from Crucell’s Ebola vaccine studies that are conducted together with the Vaccine Research Center (VRC) of the U.S. National Institutes of Health (NIH) and the U.S. Army Research Institute of Infectious Diseases (USAMRIID) have been announced. The results confirm previously published results showing that a single shot of the vaccine protected monkeys completely against a lethal Ebola challenge. These new results utilized vectors developed with Crucell's adenoviral vector and PER.C6(r) cell line technology, and show protection at lower doses than previously reported. (See Prohost Newsletter, March 2005). 

 Crucell recently secured an exclusive license to patents of the NIH for the development and commercialisation of recombinant vaccines against Ebola.

Comments: The power of the technology is everything in a biotech firm. Crucell has it. 

NARROWING LOSSES

MILLENNIUM PHARMACEUTICAL (MLNM)

Millennium Pharmaceuticals posted narrowed first-quarter losses on Thursday. As we expected, sales of Velcade climbed 51% from last year. The drug sales grew to $44.8 million for the quarter. Revenue from Integrilin, which Millennium co-promotes with Schering-Plough, was down 10% to $42.8 million. Revenue for the quarter increased 34% to $123.7 million, up from $92.6 million last year. The firm had a loss of $36.4 million, or 12 cents a share, compared with a loss of $40.6 million, or 13 cents a share, for the same quarter last year. Excluding various items, Millennium would have had an adjusted loss of 9 cents a share. Looking forward, Millennium sees 2005 Velcade sales between $185 million and $195 million. The company added that its net loss for the year should be less than $155 million.

Comments: The right track for Millennium (Read upcoming Prohost Newsletter)

Eye On

ELAN+ MLNM+CRXL+ DYAX+

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