Stroke/Harry/Nigel/Peter/Cary n Board,
Thanks for your views n input on Paion. Reg Tpa I worked in ER for a while, the major drawback I encountered was the window time period of admin ~3 hrs. Only less than 15% of ischaemic stroke pts are qualified for it and I think this will be the major adv for Desmoteplase which is upto 9 hrs.I also like Desmoteplase being studied in Pulmonary embolism. Enecadin n Solulin are long shots for Paion and are worth nothing until they show efficacy in Phase 2 but would be an awesome combo for Paion if they work out. I agree finetuning thrombolytics is boring once the rx window is expanded and I am not much enthusiastic about them.
For eg:
vernalis.com
thrombogenics.com
I was interested in a private bio Axaron which has AX200 but I am unsure of it's mechanism since they give very few details.
I like NTII defibrinogenating agent MOA better than Paion's which is a plasminogen activator but lack of efficacy in the European trials coupled with the most imp SE Intra Cranial H'age puts me off. Now the modified reduced dose doesn't give me confidence either until I see some results.I couldn't see any evidence of it in the Paion's DEDAS study though there was significant ICH (sICH) in the dose finding DIAS study.
So I am waiting for Paion's P3 results next mid year. One of my friend says this might be the reason Renovis is getting the results quicker.
investorshub.com
DIAS Study:
The Desmoteplase in Acute Ischemic Stroke Trial (DIAS)
A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase
Werner Hacke, MD; Greg Albers, MD; Yasir Al-Rawi, MD; Julien Bogousslavsky, MD; Antonio Davalos, MD; Michael Eliasziw, PhD; Michael Fischer, PhD; Anthony Furlan, MD; Markku Kaste, MD; Kennedy R. Lees, MD; Mariola Soehngen, MD Steven Warach, MD for The DIAS Study Group
From the Department of Neurology (W.H.), University of Heidelberg, Heidelberg; PAION GmbH (Y.A.-R., M.S.), Aachen; ClinResearch GmbH (M.F.), Köln, Germany; Centre Hospitalier Universitaire Vaudois (J.B.), Department of Neurology, Lausanne, Switzerland; Hospital Universitari Dr Josep Trueta (A.D.), Girona, Spain; the University of Calgary (M.E.), Heritage Medical Research Building. Calgary, Alberta, Canada; Helsinki University Central Hospital (M.K.), Department of Clinical Neurosciences, Helsinki, Finland; Western Infirmary (K.R.L.), University Department, of Medicine & Therapeutics, Glasgow, United Kingdom; the Stanford Stroke Center (G.A), Palo Alto, Calif; the Cleveland Clinic Foundation (A.F.), Department of Neurology, Cleveland, Ohio; and the National Institute of Neurological Disorders and Stroke (S.W.), Bethesda, Md.
Correspondence to Dr Werner Hacke, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail werner_hacke@med.uni-heidelberg.de
Background and Purpose— Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI.
Methods— DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 µg/kg, 90 µg/kg, and 125 µg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days.
Results— Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 µg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 µg/kg; P=0.757) and 60.0% (125 µg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion.
Conclusions— Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 µg/kg.
DEDAS study:
Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS). Evidence of Safety and Efficacy 3 to 9 Hours After Stroke Onset.
Anthony J Furlan, Dirk Eyding, Gregory W Albers, Yasir Al-Rawi, Kennedy R Lees, Howard A Rowley, Christian Sachara, Mariola Soehngen, Steven Warach, Werner Hacke
BACKGROUND AND PURPOSE: Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. METHODS: DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. RESULTS: Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022). CONCLUSIONS: Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
Regards,
Praveen |
