Results Provide Important Clinical Proof-of-Concept, Dose Response and Safety Information in the Target Patient Population
BURLINGTON, MA, USA I November 9, 2015 I Dyax Corp. (NASDAQ:DYAX) today announced that two oral presentations describing clinical data from its DX-2930 Phase 1b study were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Meeting taking place in San Antonio, Texas. DX-2930 is an investigational fully human monoclonal antibody inhibitor of plasma kallikrein (pKal) being developed for the prevention of hereditary angioedema (HAE) attacks.
“We are pleased to have our Phase 1b DX-2930 data selected for oral presentation this year at ACAAI,” said Burt Adelman, M.D., Executive Vice President of Research and Development and Chief Medical Officer at Dyax. “Collectively, these results support further clinical investigation of DX-2930 as a prophylactic treatment for HAE. We remain on track to enroll the first patient in our Phase 3 clinical trial for DX-2930 for HAE prophylaxis by year-end 2015.”
A summary of data presented is below:
Title: DX-2930 in Patients With Hereditary Angioedema: Final Results of a Phase 1b Study
Presentation No.: 49
Presenter: Joshua Jacobs, M.D., Medical Director of Allergy and Asthma Clinical Research, Allergy and Asthma Medical Group of the Bay Area and principal investigator for the DX-2930 Phase 1b study
Date and time: Monday, November 9, 2015 at 1:00pm CT
Session: Session C – Other: Pharmacology and Pharmacotherapeutics
Summary: The Phase 1b study results demonstrated that DX-2930 was well tolerated at all dose levels. There were no deaths or subject discontinuations due to an adverse event. There were no serious adverse events in subjects treated with DX-2930 and no evidence of dose-limiting toxicity. There was no safety signal in treatment-emergent adverse events, clinical laboratory results, vital signs, or electrocardiograms. Subcutaneous injection was well tolerated.
Pharmacokinetic results demonstrated that DX-2930 has linear, dose-dependent exposure and a mean elimination half-life of approximately 14 days. Pharmacodynamic results from two different exploratory biomarker assays confirmed ex vivo plasma kallikrein inhibition in a dose- and time-dependent manner.
Primary proof-of-concept efficacy analyses were based on subjects in the 300 mg, 400 mg, and placebo dose groups who reported having at least 2 attacks in the 3 months prior to study entry. During the pre-specified, primary efficacy interval of 6 weeks (from days 8 to 50; corresponding to peak drug level), the HAE attack rate (adjusted for baseline attacks) was 0 in the 300 mg group and 0.045 attacks per week in the 400 mg group, compared to 0.37 attacks per week in the placebo group. This resulted in a 100% reduction for the 300 mg dose group as compared to placebo (P < 0.0001), and an 88% reduction for the 400 mg dose group as compared to placebo (P=0.005). During this primary efficacy interval, 100% of subjects in the 300 mg group (P=0.026) and 82% of subjects in the 400 mg group (P=0.030) were attack-free compared with 27% of subjects in the placebo group.
The Phase 1b study was a multi-center, randomized, double-blind, placebo-controlled, multiple-ascending dose study. A total of 37 subjects were randomized to active drug or placebo in a 2:1 ratio across 4 dosing groups of 30, 100, 300, or 400 mg. Each subject received two doses of DX-2930 or placebo, separated by 14 days, and was followed for 15 weeks after the second dose.
Title: Attack Frequency, C1-INH Function, and Levels of Cleaved Kininogen Do Not Influence the Clinical Response to DX-2930 in Patients with Hereditary Angioedema
Presentation No.: 50
Presenter: William Lumry, M.D., Clinical Professor of Internal Medicine at the University of Texas Southwestern Medical School and principal investigator for the DX-2930 Phase 1b study
Date and time: Monday, November 9, 2015 at 1:15pm CT
Session: Session C – Other: Pharmacology and Pharmacotherapeutics
Summary: Post-hoc analyses of the Phase 1b study of DX-2930 in patients with HAE were conducted to determine if the clinical response to DX-2930 was influenced by factors such as historical attack rate, functional C1-INH levels, or the amount of cleaved (2-chain) high-molecular-weight kininogen (HMWK).
Patients were grouped by historical attack rate using data from the 3 months prior to dosing (0-0.23, 0.31-0.54, or 0.62-2.77 attacks/week). Levels of cleaved HMWK and C1-INH function were assessed by Western blot and a chromogenic assay, respectively.
C1-INH function in HAE patients ranged from 0 to 45% of normal. Neither historical nor observed attack frequency was related to baseline C1-INH levels, and baseline levels of 2-chain HMWK also did not correlate with historical attack rates. As expected, levels of 2-chain HMWK at baseline were inversely correlated with levels of functional C1-INH. It was observed that treatment with 300 or 400 mg DX-2930 reduced levels of 2-chain HMWK in a dose- and time-dependent manner, and these reductions were not influenced by historical attack rate or baseline C1-INH function. All subjects in the 300 and 400 mg does groups with high baseline attack rates (≥9 attacks in the 3 months prior to dosing) were attack-free during the Day 8 to 50 assessment period.
About DX-2930
DX-2930 is a novel, fully human monoclonal antibody inhibitor of pKal which is currently being developed as a subcutaneous injection for the prevention of HAE attacks. Uncontrolled pKal activity leads to excessive generation of bradykinin, a vasodilator thought to be responsible for the localized swelling, inflammation and pain characteristically associated with HAE.
About HAE
HAE is a rare acute inflammatory condition characterized by episodes of severe, often painful swelling affecting the extremities, gastrointestinal tract, genitalia, and larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is estimated to affect up to 1 in 50,000 individuals. Learn more at www.HAEHope.com.
About Dyax
Dyax is a biopharmaceutical company focused on the development and commercialization of novel biotherapeutics for unmet medical needs. The Company is developing DX-2930, a fully human monoclonal antibody, for the prevention of HAE attacks. Additionally, Dyax markets KALBITOR® (ecallantide) for the treatment of acute attacks of HAE in patients 12 years of age and older.
Both DX-2930 and KALBITOR were identified using Dyax’s proprietary phage display technology. Dyax has broadly licensed this technology under its Licensing and Funded Research Portfolio (LFRP). The current portfolio includes one FDA approved product, Eli Lilly and Company’s CYRAMZA® (ramucirumab), for which Dyax receives royalties, and multiple product candidates in various stages of clinical development for which the Company is eligible to receive future milestones and royalties.
SOURCE: Dyax
Post Views: 119
Results Provide Important Clinical Proof-of-Concept, Dose Response and Safety Information in the Target Patient Population
BURLINGTON, MA, USA I November 9, 2015 I Dyax Corp. (NASDAQ:DYAX) today announced that two oral presentations describing clinical data from its DX-2930 Phase 1b study were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Meeting taking place in San Antonio, Texas. DX-2930 is an investigational fully human monoclonal antibody inhibitor of plasma kallikrein (pKal) being developed for the prevention of hereditary angioedema (HAE) attacks.
“We are pleased to have our Phase 1b DX-2930 data selected for oral presentation this year at ACAAI,” said Burt Adelman, M.D., Executive Vice President of Research and Development and Chief Medical Officer at Dyax. “Collectively, these results support further clinical investigation of DX-2930 as a prophylactic treatment for HAE. We remain on track to enroll the first patient in our Phase 3 clinical trial for DX-2930 for HAE prophylaxis by year-end 2015.”
A summary of data presented is below:
Title: DX-2930 in Patients With Hereditary Angioedema: Final Results of a Phase 1b Study
Presentation No.: 49
Presenter: Joshua Jacobs, M.D., Medical Director of Allergy and Asthma Clinical Research, Allergy and Asthma Medical Group of the Bay Area and principal investigator for the DX-2930 Phase 1b study
Date and time: Monday, November 9, 2015 at 1:00pm CT
Session: Session C – Other: Pharmacology and Pharmacotherapeutics
Summary: The Phase 1b study results demonstrated that DX-2930 was well tolerated at all dose levels. There were no deaths or subject discontinuations due to an adverse event. There were no serious adverse events in subjects treated with DX-2930 and no evidence of dose-limiting toxicity. There was no safety signal in treatment-emergent adverse events, clinical laboratory results, vital signs, or electrocardiograms. Subcutaneous injection was well tolerated.
Pharmacokinetic results demonstrated that DX-2930 has linear, dose-dependent exposure and a mean elimination half-life of approximately 14 days. Pharmacodynamic results from two different exploratory biomarker assays confirmed ex vivo plasma kallikrein inhibition in a dose- and time-dependent manner.
Primary proof-of-concept efficacy analyses were based on subjects in the 300 mg, 400 mg, and placebo dose groups who reported having at least 2 attacks in the 3 months prior to study entry. During the pre-specified, primary efficacy interval of 6 weeks (from days 8 to 50; corresponding to peak drug level), the HAE attack rate (adjusted for baseline attacks) was 0 in the 300 mg group and 0.045 attacks per week in the 400 mg group, compared to 0.37 attacks per week in the placebo group. This resulted in a 100% reduction for the 300 mg dose group as compared to placebo (P < 0.0001), and an 88% reduction for the 400 mg dose group as compared to placebo (P=0.005). During this primary efficacy interval, 100% of subjects in the 300 mg group (P=0.026) and 82% of subjects in the 400 mg group (P=0.030) were attack-free compared with 27% of subjects in the placebo group.
The Phase 1b study was a multi-center, randomized, double-blind, placebo-controlled, multiple-ascending dose study. A total of 37 subjects were randomized to active drug or placebo in a 2:1 ratio across 4 dosing groups of 30, 100, 300, or 400 mg. Each subject received two doses of DX-2930 or placebo, separated by 14 days, and was followed for 15 weeks after the second dose.
Title: Attack Frequency, C1-INH Function, and Levels of Cleaved Kininogen Do Not Influence the Clinical Response to DX-2930 in Patients with Hereditary Angioedema
Presentation No.: 50
Presenter: William Lumry, M.D., Clinical Professor of Internal Medicine at the University of Texas Southwestern Medical School and principal investigator for the DX-2930 Phase 1b study
Date and time: Monday, November 9, 2015 at 1:15pm CT
Session: Session C – Other: Pharmacology and Pharmacotherapeutics
Summary: Post-hoc analyses of the Phase 1b study of DX-2930 in patients with HAE were conducted to determine if the clinical response to DX-2930 was influenced by factors such as historical attack rate, functional C1-INH levels, or the amount of cleaved (2-chain) high-molecular-weight kininogen (HMWK).
Patients were grouped by historical attack rate using data from the 3 months prior to dosing (0-0.23, 0.31-0.54, or 0.62-2.77 attacks/week). Levels of cleaved HMWK and C1-INH function were assessed by Western blot and a chromogenic assay, respectively.
C1-INH function in HAE patients ranged from 0 to 45% of normal. Neither historical nor observed attack frequency was related to baseline C1-INH levels, and baseline levels of 2-chain HMWK also did not correlate with historical attack rates. As expected, levels of 2-chain HMWK at baseline were inversely correlated with levels of functional C1-INH. It was observed that treatment with 300 or 400 mg DX-2930 reduced levels of 2-chain HMWK in a dose- and time-dependent manner, and these reductions were not influenced by historical attack rate or baseline C1-INH function. All subjects in the 300 and 400 mg does groups with high baseline attack rates (≥9 attacks in the 3 months prior to dosing) were attack-free during the Day 8 to 50 assessment period.
About DX-2930
DX-2930 is a novel, fully human monoclonal antibody inhibitor of pKal which is currently being developed as a subcutaneous injection for the prevention of HAE attacks. Uncontrolled pKal activity leads to excessive generation of bradykinin, a vasodilator thought to be responsible for the localized swelling, inflammation and pain characteristically associated with HAE.
About HAE
HAE is a rare acute inflammatory condition characterized by episodes of severe, often painful swelling affecting the extremities, gastrointestinal tract, genitalia, and larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is estimated to affect up to 1 in 50,000 individuals. Learn more at www.HAEHope.com.
About Dyax
Dyax is a biopharmaceutical company focused on the development and commercialization of novel biotherapeutics for unmet medical needs. The Company is developing DX-2930, a fully human monoclonal antibody, for the prevention of HAE attacks. Additionally, Dyax markets KALBITOR® (ecallantide) for the treatment of acute attacks of HAE in patients 12 years of age and older.
Both DX-2930 and KALBITOR were identified using Dyax’s proprietary phage display technology. Dyax has broadly licensed this technology under its Licensing and Funded Research Portfolio (LFRP). The current portfolio includes one FDA approved product, Eli Lilly and Company’s CYRAMZA® (ramucirumab), for which Dyax receives royalties, and multiple product candidates in various stages of clinical development for which the Company is eligible to receive future milestones and royalties.
SOURCE: Dyax
Post Views: 119
