Results Provide Important Clinical Proof-of-Concept, Dose Response and Safety Information in the Target Patient Population
'We are pleased to have our Phase 1b DX-2930 data selected for oral
presentation this year at ACAAI,' said
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:
Date and time:
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
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:
Date and time:
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
Both DX-2930 and KALBITOR were identified using
For additional information about
For additional information about KALBITOR, including full prescribing information, please visit www.KALBITOR.com.
Disclaimer
The press release contains forward-looking
statements, including statements regarding the prospects for therapeutic
benefits and treatment advantages of an investigational product,
DX-2930, being developed for HAE. 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
CYRAMZA
is a trademark owned by or licensed to Eli Lilly and Company, its
subsidiaries, or affiliates.
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Director,
jrobinson@dyax.com
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