DS-1040 / Daiichi Sankyo - LARVOL DELTA

Novel Deep Sea Isoindole Alkaloid FGFC1 Exhibits Its Fibrinolytic Effects by Inhibiting Thrombin-Activatable Fibrinolysis Inhibitor. (PubMed, Pharmaceuticals (Basel)) - "From the above findings, FGFC1 is identified as a novel dual-target bioactive compound participating in blood formation/dissolution that demonstrates anti-coagulation and fibrinolytic effects by regulating TAFI activation, inhibiting TAFIa-fibrin combination, and initiating proteolysis. It also provided convincing evidence that TAFI plays a critical role in thrombolysis as a molecular link between coagulation and fibrinolysis. Furthermore, the application of FGFC1 was indicated as a potential therapeutic strategy in thromboembolic and hemorrhagic diseases."

Journal • Cardiovascular • Hematological Disorders • Targeted Protein Degradation • Thrombosis

Inhibition of thrombin activatable fibrinolysis inhibitor (TAFI) via DS-1040 to accelerate clot lysis in patients with acute pulmonary embolism: a randomized phase Ib study. (PubMed, J Thromb Haemost) - "Of 125 patients with all available data, 38 were randomized to placebo and 87 to DS-1040. The primary endpoint occurred in 1 patient in the placebo group (2.6%) and 4 patients who received DS-1040 (4.6%). One subject experienced major bleeding (DS-1040 80mg group); no fatal or intracranial bleeding occurred. Thrombus volume was 25-45% lower after infusion, with no differences between DS-1040 groups and placebo. There was no difference in the change from baseline RV/LV-ratio between DS-1040 groups and placebo. In patients with acute PE, adding DS-1040 to standard anticoagulation was not associated with an increase in bleeding but did not improve thrombus resolution or RV-dilation."

Journal • P1 data • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

Safety, Pharmacokinetics and Pharmacodynamics of DS-1040, in Combination with Thrombectomy, in Japanese Patients with Acute Ischemic Stroke. (PubMed, Clin Drug Investig) - P1 | "Single doses of DS-1040 0.6-4.8 mg were well tolerated in Japanese patients with AIS undergoing thrombectomy."

Combination therapy • Journal • PK/PD data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Ischemic stroke • Pulmonary Embolism • Respiratory Diseases • Subarachnoid Hemorrhage

"Excellent presentation by Dr. Vanassche on our DS1040 trial @vic_tapson @ Menno Huisman @ hbuller @ a degree" (@RosovskyRachel)

[VIRTUAL] Inhibition of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) to Accelerate Clot Lysis in Patients with Acute Pulmonary Embolism: A Phase 2 Randomized Study (ISTH 2021) - "Methods : In this multicenter randomized double-blind placebo-controlled dose finding study, ascending doses of intravenous DS-1040 (20mg up to 80mg) were added to enoxaparin (1 mg/kg twice daily) in patients with acute PE. Conclusions : In patients with acute PE, standard anticoagulation alone resulted in a considerable reduction in thrombus volume. Adding DS-1040 was safe but did not further improve thrombus resolution."

Clinical • P2 data • Cardiovascular • Immunology • Pulmonary Embolism • Respiratory Diseases

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of DS-1040, an Inhibitor of the Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor, in Healthy Subjects. (PubMed, J Clin Pharmacol) - "Dose-dependent inhibition of total TAFIa activity was observed following single and multiple doses of oral DS-1040. The safety and PK/PD profiles of oral DS-1040 in healthy subjects support further clinical development."

Clinical • Journal • P1 data • PK/PD data • Cardiovascular • Hematological Disorders • Thrombosis

A Smart Realtime Service to Broadcast the Precise Orbits of GPS Satellite and Its Performance on Precise Point Positioning. (PubMed, Sensors (Basel)) - "For the first time in GPS, the difference in the PPP results between the precise orbits and the calculated orbits broadcasted from the generated ephemeris parameters is supplied as follows: (1) During the validity period of 2 h, root mean square (RMS) of the relative distance offsets between the results of PPP with the precise orbits and the results of PPP the 18-parameter ephemeris is only 0.0098 m. (2) Within 15 min after the validity period of 2 h, RMS of the relative distance offsets between the results of PPP with the precise orbits and the results of PPP with the predicted orbits by 18-parameter ephemeris is only 0.0057 m. Consequently, the 18-parameter ephemeris is feasible and advisable to broadcast precise predicted orbits for real-time PPP applications. Compared with the classic precise orbits broadcast mode with the orbit corrections defined by the radio technical commission for maritime services standards 10403.2 (RTCM), the mode of broadcasting the precise..."

Journal

Study of the Effects of Ethnicity on the Pharmacokinetics, Pharmacodynamics and Safety of DS-1040b (clinicaltrials.gov) - P1; N=48; Not yet recruiting; Sponsor: Daiichi Sankyo Inc.

New P1 trial • Biosimilar

A First-in-human Study of DS-1040, an Inhibitor of the Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor, in Healthy Subjects. (PubMed) - J Thromb Haemost - "The novel fibrinolysis-enhancing agent DS-1040 has favorable PK/PD properties and safety profile, which warrants further clinical development."

Journal • Biosimilar • Reperfusion Injury • Venous Thromboembolism

Safety and Pharmacokinetics of DS-1040 Drug-Drug Interactions With Aspirin, Clopidogrel, and Enoxaparin. (PubMed, J Clin Pharmacol) - P1; "When coadministered with enoxaparin, the PK parameters of DS-1040 were not affected (1.1% and 1.5% decreases in geometric means for C and AUC , respectively). Therefore, concomitant administration of DS-1040 and clopidogrel or enoxaparin did not demonstrate PK drug-drug interactions."

Clinical • Journal • PK/PD data • F2

Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy (clinicaltrials.gov) - P1; N=42; Completed; Sponsor: Daiichi Sankyo Co., Ltd.; Active, not recruiting ➔ Completed; N=60 ➔ 42; Trial completion date: Jun 2020 ➔ Jan 2020

Clinical • Enrollment change • Trial completion • Trial completion date • F2

Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy (clinicaltrials.gov) - P1; N=60; Active, not recruiting; Sponsor: Daiichi Sankyo Co., Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • F2

ASSENT: Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1b/2; N=106; Completed; Sponsor: Daiichi Sankyo, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ Aug 2019; Trial primary completion date: Aug 2019 ➔ May 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

Randomized Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism (clinicaltrials.gov) - P1b; N=134; Completed; Sponsor: Daiichi Sankyo, Inc.; Recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ Aug 2019

Clinical • Trial completion • Trial completion date

ASSENT: Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1b/2; N=130; Active, not recruiting; Sponsor: Daiichi Sankyo, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

ASSENT: Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke (clinicaltrials.gov) - P1b/2; N=130; Recruiting; Sponsor: Daiichi Sankyo, Inc.; Trial completion date: May 2019 ➔ Nov 2019; Trial primary completion date: May 2019 ➔ Aug 2019

Clinical • Trial completion date • Trial primary completion date

Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Daiichi Sankyo Co., Ltd.; Trial completion date: Sep 2019 ➔ Jun 2020; Trial primary completion date: Jun 2019 ➔ Apr 2020

Clinical • Trial completion date • Trial primary completion date

Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Daiichi Sankyo Co., Ltd.; Trial completion date: Jun 2019 ➔ Sep 2019; Trial primary completion date: Mar 2019 ➔ Jun 2019

Clinical • Trial completion date • Trial primary completion date

Randomized Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism (clinicaltrials.gov) - P1b; N=137; Recruiting; Sponsor: Daiichi Sankyo, Inc.; Trial completion date: Jul 2019 ➔ Nov 2019; Trial primary completion date: Jan 2019 ➔ Aug 2019

Clinical • Trial completion date • Trial primary completion date