Replies to post #69846 on Biotech Values

[DewDiligence]

Daiichi Sankyo’s oral FXa inhibitor, DU-176b, is now called Edoxaban:

http://finance.yahoo.com/news/Edoxaban-Factor-Xa-Inhibitor-prnews-14763498.html

[DewDiligence]

Daiichi Sankyo Starts Phase-3 Trial of Edoxaban in VTE Prevention

[Edoxaban (f/k/a/ DU-176b) is an oral FXa inhibitor similar to Xarelto (from Bayer/JNJ) and apixaban (from BMY/PFE). Edoxaban has had a much lower profile than Xarelto and apixaban, which may be attributable to the fact that investors pay more attention to US-based Big Pharma than to Japanese companies.

The phase-3 trial that’s the subject of this PR will test edoxaban vs warfarin for one year following acute-care Lovenox/UFH to treat a VTE episode. The primary endpoint will be the rate of VTE recurrence at one year. This trial builds on the phase-2 success of a head-to-head study of edoxaban vs Fragmin in VTE prevention following hip surgery (#msg-31950663).

This is the first phase-3 trial of edoxaban in VTE prevention; an even larger phase-3 edoxaban trial of 16,500 patients is underway in AF (#msg-34100821).]

http://finance.yahoo.com/news/Daiichi-Sankyo-Initiates-prnews-1785968700.html?x=0&.v=1

›Daiichi Sankyo Initiates Largest Single, Double-Blind, Randomized, Phase III Trial for Treatment and Prevention of Recurrent Venous Thromboembolism

Wednesday February 3, 2010, 8:00 am

TOKYO and EDISON, N.J., Feb. 3 /PRNewswire/ -- Daiichi Sankyo Company, Limited (TSE: 4568), announced today that it has initiated a new large-scale pivotal Phase III trial for edoxaban, its investigational oral Factor Xa inhibitor. This new study, called HOKUSAI (pronounced hoe·koo·sigh) VTE, is evaluating the safety and efficacy of edoxaban in reducing recurrent venous thromboembolic (VTE) complications in patients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

It is estimated that more than 900,000 fatal and non-fatal VTE events occur in the U.S. annually, and approximately 300,000 deaths are related to VTE per year. In Europe, VTE affects more than 750,000 people in six major European countries (France, Germany, Italy, Spain, Sweden, UK) annually, and approximately 370,000 deaths are related to VTE per year in these countries.

"The incidence of VTE is predicted to double by 2050," said Harry R. Buller, M.D., Professor of Internal Medicine, chairman of the Department for Vascular Medicine at the Academic Medical Center, Amsterdam and chairman of the Steering Committee for HOKUSAI VTE. "Based on what we've seen in Phase II and other trials, edoxaban shows promise as an agent to help fulfill the need for treatment options that are safe, effective and more convenient than the current standard of care, which requires extensive monitoring, careful dose adjusting and may have the potential for various drug and food interactions."

The primary efficacy endpoint for HOKUSAI VTE is the recurrence of symptomatic VTE (i.e., the composite of DVT, non-fatal PE and fatal PE). The primary safety assessment of the trial is the incidence of major and clinically relevant non-major bleeding.

"HOKUSAI VTE is the largest, single Phase III study ever undertaken in the area of VTE, and is our second large-scale edoxaban trial," said Glenn Gormley, president of Daiichi Sankyo Pharma Development. "Daiichi Sankyo is proud to be advancing the research of Factor Xa inhibitors with edoxaban, which may help prevent deadly clots in various patient populations."

HOKUSAI VTE Study Design

HOKUSAI VTE is a Phase III multi-center study that will include approximately 7,500 patients in more than 450 clinical sites in approximately 40 countries worldwide. This is an event-driven, randomized, double-blind, double-dummy, parallel-group, multi-center, multi-national study, which will randomize patients to two different treatment groups. Both groups will receive open label enoxaparin or unfractionated heparin for at least five days and up to 12 days, followed by double-blind warfarin or edoxaban 60 mg once-daily. Patients will be treated for up to 12 months in accordance to the standard of care and international guidelines.

The HOKUSAI VTE study is named after the famous Japanese artist and painter Katsushika Hokusai (1760-1849) of the former Edo period; Edo is the city currently known as Tokyo, the location of the Daiichi Sankyo global headquarters.

About Venous Thromboembolism

Venous thromboembolism (VTE) is the term for the generation of a blood clot and the obstruction of a vein or a pulmonary artery by a blood clot. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are types of VTE. DVT is a blood clot anywhere in the deep veins of the legs or pelvis. PE is caused by a clot that travels to the lungs, lodging in the pulmonary arteries.

About Edoxaban

Edoxaban, the free base of DU-176b, is an oral anticoagulant that directly inhibits Factor Xa, an important factor in the coagulation process. Daiichi Sankyo is developing edoxaban as a potential new treatment for the prevention of both arterial and venous thromboembolism. Notably, Daiichi Sankyo has more than 25 years experience conducting research in the area of Factor Xa inhibition, and was the first company to study these compounds in humans. Edoxaban is being developed solely by Daiichi Sankyo.

Daiichi Sankyo is also actively enrolling 16,500 patients in its pivotal Phase III trial for edoxaban in patients with atrial fibrillation. The Phase III study, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE AF-TIMI 48), began enrolling patients in late 2008 and is comparing edoxaban with warfarin (target INR 2-3) for the prevention of stroke and systemic embolic events (SEE) among patients with atrial fibrillation.

In Japan, edoxaban is currently being developed for the prevention of VTE in patients after total knee (TKR) and total hip replacement (THR) surgery: results from one pivotal Phase III trial for TKR were announced in late 2009 and a second Phase III trial for THR is ongoing.

About Daiichi Sankyo

A global pharmaceutical innovator, Daiichi Sankyo Co., Ltd., was established in 2005 through the merger of two leading Japanese pharmaceutical companies. This integration created a more robust organization that allows for continuous development of novel drugs that enrich the quality of life for patients around the world. Areas of central focus of Daiichi Sankyo research and development are thrombotic disorders, malignant neoplasm, diabetes mellitus and autoimmune disorders. Equally important to the company are hypertension, hyperlipidemia or atherosclerosis and bacterial infections. For more information, visit www.daiichisankyo.com.‹

[DewDiligence]

Daiichi Sankyo Enrolls 21,107(!) Patients in Edoxaban AF Trial

[Edoxaban (f/k/a DU-176b) is an oral FXa inhibitor similar to Xarelto and Apixaban, both of which have shown statsig phase-3 efficacy for stroke prevention in AF. Like Xarelto, Edoxaban has the advantage of qD dosing, but it has the drawback of requiring dose reduction in some patients with renal impairment, as is the case with Pradaxa (#msg-56742484).

The phase-3 trial that’s the subject of this PR started in Dec 2008 and is expected to finish in 1H12 (#msg-34100821); it was originally slated to have 16,500 patients, but the number somehow ballooned to 21,000+. Rather than following patients for a fixed time, this trial is event-driven, i.e. it proceeds until a prespecified number of stroke/embolism events have occurred in all arms combined. The trial is double-blinded and the comparator is warfarin, which means that clinicians perform faux warfarin monitoring for patients in the Edoxaban arms. This makes the trial more cumbersome to conduct, but it preempts the criticism of the pivotal trial for Pradaxa for being open-label.

Phase-2 data for Edoxaban in AF are in #msg-34100787.]

http://finance.yahoo.com/news/Daiichi-Sankyo-Completes-prnews-1332657057.html?x=0&.v=1

›Daiichi Sankyo Completes Enrollment of the Edoxaban Global Phase III ENGAGE AF-TIMI 48 Study in Patients With Atrial Fibrillation

More than 21,000 Patients Enrolled in the Largest Clinical Study with a Factor Xa Inhibitor

Wednesday December 1, 2010, 8:30 am EST

PARSIPPANY, N.J., Dec. 1, 2010 /PRNewswire-FirstCall/ -- Daiichi Sankyo Company, Limited (TSE:4568.to - News) announced today that it has successfully completed patient enrollment for its Phase III ENGAGE AF-TIMI 48 clinical study of edoxaban, a direct, specific, oral Factor Xa inhibitor that is being investigated in two different dosing regimens given once daily, to prevent the occurrence of strokes and systemic embolic events (SEE) in patients with atrial fibrillation (AF).

An estimated 2.2 million Americans suffer from AF, and about 90,000 strokes in the U.S. each year are caused by AF. Due to the aging population, the number of patients with AF worldwide is likely to increase 2.5-fold by the year 2050.

The ENGAGE AF-TIMI 48 study began enrollment in November 2008. It is an event-driven, randomized, double-blind, double-dummy, parallel group, multi-center, multi-national study designed to assess the efficacy and safety of edoxaban compared to the current standard of care, warfarin. Patients in the study are randomized to one of three treatment groups: 30 mg edoxaban once daily, 60 mg edoxaban once daily, or warfarin, a vitamin K antagonist. In addition, edoxaban doses are further adjusted to treat patients with renal impairment and/or low body weight, or those taking strong P-glycoprotein inhibitors. Those randomized to warfarin are dosed once daily to achieve an International Normalized Ratio (INR) between 2.0 and 3.0.

"The completion of enrollment for the largest AF outcomes study ever undertaken -- ENGAGE AF-TIMI 48 -- marks a key milestone in the development of edoxaban and for Daiichi Sankyo," said Glenn Gormley, MD, PhD, Chief Science Officer & President, Daiichi Sankyo Pharma Development.

This Phase III global AF study, Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE AF-TIMI 48), enrolled 21,107 subjects at nearly 1,400 clinical trial sites located throughout North America, South America, Africa, Asia, Europe and Australia/New Zealand. The primary endpoint of this study is to compare the efficacy of edoxaban to warfarin in the prevention of stroke and SEE [Systemic Embolic Events]. The primary safety assessment is the incidence of major bleeding events.

"As new options to prevent stroke in AF patients become available, it will be important that these treatments eliminate the need for extensive monitoring and dietary modifications," said Elliott Antman, MD, Professor of Medicine, Harvard Medical School, Senior Investigator with the Brigham and Women's Hospital-based TIMI Study Group. "Based on Phase II study results, edoxaban has shown promise of potentially addressing the needs of patients with AF and the physicians caring for them."‹