Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study

Article

Author: Lumry, William ; Longhurst, Hilary J ; Bernstein, Jonathan ; Riedl, Marc A ; Cicardi, Marco ; Li, H Henry ; Bork, Konrad ; Baker, James ; Pragst, Ingo ; Zuraw, Bruce ; Prusty, Subhransu ; Craig, Timothy ; Levy, Donald ; Feuersenger, Henrike ; Manning, Michael ; Machnig, Thomas

AbstractBackgroundHereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment effects by subgroups, onset of effect, and other exploratory analysis have not been reported.MethodsThis is a post hoc exploratory analysis on data from the randomized, placebo-controlled COMPACT study. 90 patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH (SC) 40 or 60 IU/kg of body weight twice weekly for 16 weeks, preceded or followed by a placebo period. The pre-specified primary efficacy endpoint was the time-normalized number of HAE attacks, and pre-specified secondary efficacy endpoints were the percentage of patients with a certain treatment response (≥ 50% reduction on C1-INH (SC) versus placebo in the time-normalized number of attacks) and the time-normalized number of use of rescue medication. Pre-specified exploratory endpoints included severity of attacks, alone and combined with rescue medication use. Post hoc analyses included exploration of onset of effect and clinical assessment of patients with < 50% of response.ResultsSubgroup findings by various patient characteristics showed a consistent preventive effect of C1-INH (SC). In a post hoc analysis of attacks, the onset of the preventive effect within the first 2 weeks after treatment initiation in COMPACT showed that 10/43 patients (23%) experienced attacks of any severity with 60 IU/kg versus 34/42 patients (81%) with placebo. The need for rescue medication was tenfold lower with 60 IU/kg (35 treated attacks) versus placebo (358 treated attacks). A qualitative analysis of the 4 patients treated with 60 IU/kg and with < 50% reduction of attacks demonstrated a reduction in severity of attacks, rescue medication use, and symptom days which was considered a clinically meaningful treatment effect.ConclusionsC1-INH (SC) prophylaxis demonstrated a preventive treatment effect with evidence of benefit within 2 weeks. A consistent treatment effect at recommended C1-INH (SC) dosing was evident in all subgroups of patients with type I/II HAE and by various measures of disease and treatment burden.Trial registration EU Clinical Trials Register, 2013-000916-10, Registered 10 December 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000916-10; ClinicalTrials.gov Register, NCT01912456, Registered 31 July 2013, https://clinicaltrials.gov/ct2/show/NCT01912456.

01 Dec 2013·World Journal of Emergency SurgeryQ2 · MEDICINE

Off-pump suture repair of left ventricular rupture utilizing TachoComb® sheet: a case report and literature review

Q2 · MEDICINE

ArticleOA

Author: Tatsuya Nakao ; Hiromasa Nakamura ; Masami Takagaki ; Noriyuki Tokunaga ; Hiroki Yamaguchi

A 70-year-old woman was admitted to our institution with acute myocardial infarction. Coronary angiography demonstrated total occlusion of the left anterior descending artery, which was successfully revascularized. Four days later, the patient suddenly went into shock. The subsequent emergency operation revealed a blowout rupture of the left ventricular free wall. Several TachoComb® (CSL Behring, Tokyo, Japan) sheets were applied to control bleeding and avoid the need for a cardiopulmonary bypass. Horizontal mattress sutures were used in combination with a pair of Teflon felt strips for reinforcement. The combination of TachoComb® sheets and sutures is a novel hybrid method and an effective life-saving procedure for the treatment of left ventricular blowout ruptures. This approach avoids the need for a cardiopulmonary bypass. Sutureless repairs with TachoComb® sheet achieve rapid hemostasis without the need for cardiopulmonary bypass. This stabilizes patient hemodynamics immediately and preserves the fragile myocardium. This allows emergency room physicians to open the chest and apply the TachoComb® sheet to stabilize the patient before the cardiac surgeons arrive at the operating room. This technique will be very useful in emergency situations.

01 Feb 2013·Nature MedicineQ1 · MEDICINE

The clot thickens for long-lasting drugs that stop hemophilia short

Q1 · MEDICINE

Author: Opar, Alisa

If approved, the products are expected to cut into the $5 billion global market for factor VIII therapies and the $1 billion market for factor IX drugs.Yet the Biogen agents might soon have competition in the long-acting arena.On 7 Jan., Baxter launched a 146-person trial assessing a version of clotting factor VIII attached to a polyethylene glycol (PEG) residue.This process, known as PEGylation, increases the size of the factor protein mol., which prevents the kidneys from clearing it and allows the drug to last longer in the blood.In phase 1 trials, the half-life of the exptl. Baxter drug, dubbed BAX855, was about 1.5 times higher than the company′s current bestseller Advate, putting its stability on par with that of Biogen′s BIIB029.Similarly, Denmark′s Novo Nordisk and New Jersey′s Bayer HealthCare are in the final stages of clin. tests of PEGylated clotting factor therapies, while Pennsylvania′s CSL Behring has a fusion protein that links the blood serum protein albumin to factor IX for added stability.Early studies indicate that some PEGylated and albumin-bound products may outlast Biogen′s Ig fragment-tagged therapies, but phase 3 data aren′t yet available.All these drug options, if approved, could be a boon for patients like the MacDonald boys. "Having multiple options is important," says Margaret Ragni, director of the Hemophilia Center of Western Pennsylvania in Pittsburgh who has tested Biogen′s new agents. "With hemophilia, one size doesn′t always fit all." "Keep your eyeball on gene therapy, too," notes Pipe.In 2011, clinicians at University College London, using a gene therapy product developed by researchers at St.Jude Children′s Research Hospital in Memphis, Tennessee, made a big splash when they successfully treated six patients with hemophilia B by injecting them with the correct form of a defective gene (N. Engl. J. Med.365, 2357-2365, 2011).Pipe estimates it will take another five to ten years to bring gene therapy for hemophilia B to market, with hemophilia A farther behind because of the difficultly of expressing factor VIII.Still, he says, "everyone sees gene therapy as the way forward for an ultimate cure for hemophilia."

100 Deals associated with Factor XP Behring(CSL Behring LLC)

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	B02BD	-

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hemophilia B	ES	CSL Behring LLC	21 Sep 2015
Factor X Deficiency	ES	CSL Behring LLC	01 Sep 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Factor XP Behring(CSL Behring LLC)

Overview

Basic Info

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation