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Analysis also reveals decrease in emergency room visits and hospitalizations
San Diego, CA — 01 March 2014
Findings announced by CSL Behring today show that current hereditary angioedema (HAE) treatment options, such as C1 Esterase Inhibitor (C1-INH) concentrate, are allowing for greater patient satisfaction, higher rates of home treatment and a decrease in the number of hospitalizations and visits to the emergency room. HAE is a rare, potentially fatal swelling disorder caused by a deficiency of C1-INH. Until recently, only limited therapeutic options were available for patients in the U.S. with the condition. Today, HAE patients can choose from multiple options to address their condition. The 46-question online survey of physicians, which was conducted between March and June 2013, closely patterned after an initial survey conducted between October 2009 and February 2010. The data were presented at the 2014 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.
“The previously conducted survey revealed wide variability in HAE management, leaving questions about the impact of newer treatment options and changes in HAE care,” said Marc A. Riedl, MD, MS, Associate Professor of Medicine and Section Head of Clinical Immunology and Allergy at the UCLA David Geffen School of Medicine, and one of the study’s investigators. “As our results have shown, current treatment practices now align more closely with current HAE treatment guidelines, with patients demonstrating an increase in satisfaction and physicians noticing improved patient outcomes.”
Current HAE guidelines from the World Allergy Organization recommend that all acute attacks be considered for on-demand treatment, and that such treatment be mandatory for attacks affecting upper airways. The guidelines further state that on-demand treatment be given as early in the attack as possible. According to study findings, there was a three-fold increase in the percentage of attacks self-treated at home (8 percent to 27 percent; P<0.00005). Additionally, the study found convenience was reported more frequently as an important treatment decision driver for patients (27 percent versus 10 percent; P<0.00005). Based on these treatment strategies, the percentage of patients perceived by physicians to be very satisfied with HAE treatment increased from 13 percent to 40 percent (P<0.00005).
Additional findings note that preferences toward danazol, an often-used steroid treatment, have decreased from 56 percent to 23 percent (P<0.00005). Decreases were also observed in HAE attack-related emergency room visits (62 percent to 54 percent; P=NS) and hospitalizations (13 percent to 3 percent; P=0.0001).Read full article
BURLINGTON, Mass.–(BUSINESS WIRE)– Dyax Corp. (NASDAQ:DYAX) today announced positive results from the first-in-human clinical study of their investigational product, DX-2930. The Phase 1a study met all objectives of assessing safety, tolerability and pharmacokinetics of DX-2930. Discovered by Dyax, DX-2930 is a fully human monoclonal antibody inhibitor of plasma kallikrein being developed for the prevention of hereditary angioedema (HAE) attacks.
The study was a randomized, double-blind, placebo-controlled, single dose escalating trial in healthy subjects. Subjects received a single dose of DX-2930 [0.1, 0.3, 1.0, or 3.0 mg/kg] or placebo by subcutaneous injection, with 6 subjects receiving active drug and 2 subjects receiving placebo per dose level. A total of 32 subjects were enrolled, randomized, and dosed.
Study results demonstrated that DX-2930 was well tolerated at all dose levels. There were no serious adverse events or evidence of dose-limiting toxicity. Headache was the most commonly reported adverse event and occurred at a rate of 25% in both the DX-2930 and placebo dose groups.
Pharmacokinetic results demonstrated that DX-2930 has linear, dose-dependent exposure and a mean elimination half-life of 17 to 20 days across dose groups, following a single injection to healthy subjects. Pharmacodynamic results from two different exploratory biomarker assays confirmed ex vivo plasma kallikrein inhibition in a dose and time dependent manner.
The safety, tolerability, pharmacokinetic and plasma kallikrein inhibition results of the Phase 1a study support advancing the DX-2930 development program into a Phase 1b study mid-2014. The Phase 1b study will be a randomized, double-blind, repeat-dose, dose-escalation study conducted at multiple sites to evaluate DX-2930 in patients with HAE.
“We are very excited by the study results,” said Burt Adelman, M.D., Executive Vice President and Chief Medical Officer at Dyax. “With these results we continue to be impressed by DX-2930 and are encouraged that our scientific hypotheses are on track. We look forward to initiating our Phase 1b study of DX-2930 in HAE patients in mid-2014.”
“The successful completion of this study is an important milestone for Dyax and the DX-2930 development program,” said Gustav Christensen, President and Chief Executive Officer of Dyax. “Given prior validation of the plasma kallikrein pathway in HAE, we believe DX-2930 has the potential to be a game changer in HAE therapy.”Read full article
KING OF PRUSSIA, Pa., Feb. 20, 2014 /PRNewswire/ — CSL Behring today announced it has enrolled the first patient in COMPACT, an international phase III study of a volume-reduced, subcutaneous formulation of C1-esterase inhibitor (C1-INH) concentrate in patients with frequent hereditary angioedema (HAE) attacks (NCT01912456). This phase of the COMPACT program will assess the efficacy and safety of a new formulation of the CSL Behring C1-INH concentrate in preventing hereditary angioedema attacks when the therapy is administered twice weekly under the skin (i.e., subcutaneously) of patients diagnosed with HAE.
COMPACT is an acronym for Clinical Studies for Optimal Management in Preventing Angioedema with Low-Volume Subcutaneous C1-inhibitor Replacement Therapy).
“To date, COMPACT has shown that various doses of this volume-reduced formulation of C1-INH concentrate are well tolerated when administered at a single infusion site twice weekly,” said Bruce Zuraw, MD, Professor of Medicine at the University of California, San Diego, USA, and Chairman of the Steering Committee for the COMPACT program. “We also observed a dose-dependent, physiologically relevant increase in functional C1-INH plasma levels. From a clinical perspective, these results are intriguing and could lead to a more convenient option for people with HAE.”
The COMPACT phase III, double-blind, randomized, placebo-controlled, cross-over study enrolls adolescent and adult patients with HAE types I or II who have frequent attacks. The study will measure the number of hereditary angioedema attacks that subjects experience while receiving each treatment. Subjects will be able to take on-demand medication for acute attacks at any time during the study.
“The COMPACT study is an important demonstration of the commitment CSL Behring has to the HAE community,” said Russell Basser, Senior Vice President of Clinical Research and Development at CSL Behring. “CSL Behring has been a leader in this area for decades, so we are confident that our current efforts to develop a safe, effective and convenient new treatment option for HAE patients will be successful.”
Additional information about the COMPACT trial and participating centers can be found here: http://clinicaltrials.govRead full article
RESEARCH TRIANGLE PARK, N.C.–(BUSINESS WIRE)– BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced that it has selected two optimized plasma kallikrein inhibitors to advance into preclinical development as potential once-daily, oral treatments for the prevention of hereditary angioedema (HAE) attacks.
The second generation discovery program’s goals of improving selectivity and bioavailability compared to BCX4161 were both met, with no effect on prothrombin time at high concentrations ( > 50 micromolar), and oral fraction absorbed exceeding 25%. Similar to BCX4161, these BioCryst discovered compounds demonstrate sub-nanomolar potency on the isolated enzyme and single digit nanomolar potency in suppressing kallikrein activity in an ex vivo activated human plasma kallikrein inhibition (aPKI) assay. Plasma concentrations of each of the optimized compounds exceeded the aPKI assay EC80 concentration at 24 hours after a single oral dose of 10 mg/kg in rats, indicating suitability for once-daily dosing.
“We are pleased with the outcome of our discovery program for second-generation plasma kallikrein inhibitors,” said Yarlagadda S. Babu, Ph.D., Senior Vice President, Drug Discovery at BioCryst. “We look forward to evaluating nonclinical safety in the preclinical development phase, and to providing updates regarding our progress towards our goal of developing a once-daily prophylactic therapy for hereditary angioedema.”
Discovered by BioCryst, BCX4161 is a novel, selective inhibitor of plasma kallikrein in Phase 2 development for prevention of attacks in patients with hereditary angioedema. By inhibiting plasma kallikrein, BCX4161 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.Read full article
BURLINGTON, Mass.–(BUSINESS WIRE)– Dyax Corp. (NASDAQ:DYAX) today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to its drug candidate DX-2930, its fully human monoclonal antibody inhibitor of plasma kallikrein, for use in the treatment of hereditary angioedema (HAE).
Dyax is developing DX-2930 to be a long-acting, prophylactic agent that prevents HAE attacks. Development plans include a dosage formulation that will permit infrequent self-administration by small volume, subcutaneous injection. DX-2930 is currently being studied in a placebo-controlled, dose-escalation Phase 1 trial in normal individuals. Results from this study are expected in the first quarter of 2014.
“Through our experience in the development and commercialization of KALBITOR® (ecallantide), we have gained a deep understanding of the HAE market and patient needs,” said Gustav Christensen, President and Chief Executive Officer of Dyax. “There is still a significant unmet medical need within the HAE community which we plan to address with DX-2930. Orphan drug designation is an important element of our development strategy for DX-2930 as we work to further improve the health and quality of life for individuals suffering from this painful and often debilitating condition.”
Orphan drug designation is granted by the FDA Office of Orphan Drug Products to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 patients in the U.S. The designation provides FDA assistance in clinical trial design, an exemption from FDA user fees and eligibility for a seven-year period of market exclusivity in the U.S. after product approval.Read full article