Biotech Values

[DewDiligence]

Daiichi Sankyo Presents Positive Phase-3 Data on Edoxaban in VTE Prevention

[Edoxaban (f/k/a/ DU-176b) is an oral FXa inhibitor similar to Xarelto and Eliquis that is already approved in Japan for VTE prevention following hip/knee surgery based on the data described below (#msg-62357482). Although Daiichi Sankyo plans to commercialize Edoxaban globally, the program outside of Asia is so far behind the comparable programs for Xarelto and Eliquis that I question whether Edoxaban can catch up. Among the phase-3 trials that Daiichi is running are one in secondary VTE prevention (#msg-46218043) and one in AF/stroke prevention (#msg-57277975); the comparator in both cases is warfarin.

In the two phase-3 studies described below, which were conducted in Japan and Taiwan, the comparator was Lovenox, but Lovenox was dosed at only 20mg/day, which is much below the typical dose used in the US and Europe. Moreover, in these studies Lovenox treatment was started about a day later than Edoxaban treatment, so one could almost say that the studies were rigged to show an efficacy benefit for the Edoxaban arms. These features of the studies make it hard to extrapolate the outcomes to the global market; in any case, I do not expect Exoxaban to be a significant player in the US market, so no changes to the arithmetic in #msg-69173426 are warranted on account of these data, IMO.]

http://finance.yahoo.com/news/Edoxaban-Significantly-prnews-1418468564.html?x=0

›Edoxaban Significantly Reduces Risk of Venous Thromboembolism by Half Compared to Enoxaparin in Japanese and Taiwanese Patients Following Knee or Hip Arthroplasty Surgery

Pooled results of the STARS E-III and STARS J-V studies presented at the 2011 American Society of Hematology (ASH) Annual Meeting

TOKYO and SAN DIEGO , Dec. 12, 2011 /PRNewswire/ -- Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced the results of a pooled analysis showing that edoxaban, a direct oral once-daily Factor Xa inhibitor, significantly reduced the risk of developing venous thromboembolism (VTE) following total knee or hip arthroplasty, when compared to enoxaparin. Patients receiving edoxaban had a lower incidence of a composite of deep vein thrombosis (DVT) and pulmonary embolism (PE) than those treated with enoxaparin (5.1 percent vs. 10.7 percent, P<0.001, Relative Risk Reduction [RRR] 52.7 percent), an effect that was shown without a statistically significant difference in bleeding between the groups [but Edoxaban had a numerically higher bleeding rate].

The analysis drew data from two randomized, double-blind, double-dummy, Phase III studies (STARS E-III and STARS J-V) of 1,326 Japanese and Taiwanese patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA). Results were presented in an oral session at the 53rd Annual Meeting of the American Society of Hematology in San Diego , USA.

"Total hip and knee arthroplasty surgeries place patients at a higher risk of DVT, which can lead to thromboembolic disease such as PE," said Dr. Takeshi Fuji , Head of Orthopedic Surgery, Osaka Koseinenkin Hospital, Osaka, Japan . "As the number of these surgeries increases, and the incidence of VTE is expected to double by the year 2050, it will become increasingly important for physicians to have a number of treatment options to prevent DVT and PE following these surgeries."[iv]

The incidence of major and Clinically Relevant Non-Major (CRNM) bleeding events in the edoxaban and enoxaparin groups was 4.6 percent vs. 3.7 percent, respectively (P=0.427). A further subgroup analysis of major and CRNM bleeding indicated no significant difference between edoxaban and enoxaparin in any of the patient subgroups evaluated, based on age, weight, or creatinine clearance.

Patients enrolled in the STARS E-III (Japanese and Taiwanese patients) and STARS J-V (Japanese patients) studies were randomized to receive either oral edoxaban 30 mg once daily or subcutaneous enoxaparin 20 mg (2,000 IU) twice daily for 11 to 14 days, in line with standard clinical practice in Japan.

"We are pleased to see positive outcomes with edoxaban in this patient population," said Dr. Kazunori Hirokawa , Global Head of R&D Unit, Daiichi Sankyo Co., Ltd. "These results further support the safety and efficacy of edoxaban in the prevention of DVT and PE following major orthopedic surgery. Daiichi Sankyo remains committed to developing edoxaban in our global clinical trials program."

About Edoxaban

Edoxaban is a once-daily oral anticoagulant that directly inhibits Factor Xa, an important factor in the coagulation process. Edoxaban is currently available only in Japan , licensed for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty, total hip arthroplasty and hip fracture surgery. Daiichi Sankyo continues to develop edoxaban at a global level as a potential new treatment for stroke prevention in atrial fibrillation, and the treatment and prevention of recurrent VTE. 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.

About the Pooled STARS Analysis

The analysis drew data from two Phase III comparative studies, STARS E-III and STARS J-V.

• The STARS E-III study was a double-blind, enoxaparin-controlled, randomized study comparing edoxaban 30 mg once daily and enoxaparin 20 mg (2,000 IU) in the prevention of VTE in a total of 716 Japanese and Taiwanese patients undergoing TKA.

• The STARS J-V study was a double-blind, enoxaparin-controlled, randomized study comparing edoxaban 30 mg once daily and enoxaparin 20 mg (2,000 IU) in the prevention of VTE in 610 Japanese patients undergoing THA.

Both studies supported the March 2010 edoxaban New Drug Application (NDA) in Japan seeking approval for the prevention of VTE after major orthopedic surgery. In the studies, edoxaban was initiated six to 24 hours after surgery; enoxaparin was initiated 24 to 36 hours after surgery, the standard of care in Japan . The primary efficacy outcome in both studies was the composite of symptomatic and asymptomatic DVT and PE. The principal safety outcome was incidence of major and clinically relevant non-major bleeding.‹