Biotech Values

[DewDiligence]

Xience Superiority to Taxus Continues to 2 Years

[These data are from the SPIRIT IV trial, which was a large (~4,000 patients) “real world” head-to-head study of ABT’s Xience vs BSX’s Taxus in which the primary endpoint was TLF (Target Lesion Failure, a composite of cardiac death, MI in the target vessel, and revascularization of the target vessel) at one year. The one-year data, reported in Oct 2009, showed Xience had a TLF hazard ratio of 0.61 with a p-value of 0.0008 (see KM plots in #msg-42404723). At two years, Xience continued to be statisg better than Taxus with a TLF hazard ratio of 0.70 and a p-value of 0.003.

Since Xience’s HR at two years (0.70) was not quite as good as the HR at one year (0.61), BSX may try to claim that the superiority of Xience wanes over time. Good luck to them if they attempt to pursue that argument! All told, I see nothing in these new data to suggest that Taxus is capable of reversing its slow but steady decline to irrelevance.]

http://finance.yahoo.com/news/Abbotts-XIENCE-V-Shows-prnews-1368474665.html?x=0&.v=1

›September 23, 2010, 11:34 am

ABBOTT PARK, Ill., Sept. 23 /PRNewswire-FirstCall/ -- Late-breaking data from the SPIRIT IV trial, one of the largest randomized clinical trials between two drug eluting stents, continued to demonstrate outstanding clinical results of Abbott's (NYSE:ABT) market-leading XIENCE V® Everolimus Eluting Coronary Stent System versus the TAXUS® Express2™ Paclitaxel-Eluting Coronary Stent System (TAXUS) in key areas of safety and efficacy through two years. The impressive two-year results were presented today by Gregg W. Stone, M.D., professor of medicine at Columbia University Medical Center and New York-Presbyterian Hospital, during the Cardiovascular Research Foundation's 22nd annual Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington, D.C.

In the trial's composite endpoint, XIENCE V demonstrated a clinically significant 30 percent risk reduction in TLF (target lesion failure) compared to TAXUS (6.9 percent for XIENCE V vs. 9.9 percent for TAXUS, p-value=0.003). TLF is a composite measure of important efficacy and safety outcomes for patients and is defined as cardiac death, heart attack attributed to the target vessel (target vessel myocardial infarction), and ischemia-driven target lesion revascularization (ID-TLR). XIENCE V also demonstrated a clinically significant 34 percent risk reduction in ID-TLR (repeat procedure) compared to TAXUS (4.5 percent for XIENCE V vs. 6.9 percent for TAXUS, p-value=0.004). ID-TLR is one of the major secondary endpoints of the SPIRIT IV trial.

"The two-year results from SPIRIT IV show that XIENCE V significantly reduces a patient's risk of experiencing a heart attack, stent thrombosis and the need for a repeat procedure," said Dr. Stone, principal investigator of the SPIRIT IV trial. "These are important measures of safety that have a major impact on the lives of the millions of patients who receive a drug eluting stent every year. The positive SPIRIT IV data at two years continue to demonstrate superior safety and efficacy of the XIENCE V stent platform."

In addition to demonstrating clinically significant results for TLF and ID-TLR, XIENCE V had an impressive low rate of stent thrombosis through two years. Per protocol definition, XIENCE V demonstrated a 70 percent risk reduction in stent thrombosis compared to TAXUS (0.33 percent for XIENCE V vs. 1.25 percent for TAXUS, p-value=0.002) through two years. Per Academic Research Consortium (ARC) definition of definite/probable stent thrombosis, XIENCE V demonstrated a 64 percent risk reduction through two years (0.42 percent for XIENCE V and 1.23 percent for TAXUS, p-value=0.008). The ARC definitions of stent thrombosis were developed to harmonize the definition of stent thrombosis across various drug eluting stent trials.

Key Results from the SPIRIT IV Trial

In the SPIRIT IV trial of 3,690 patients, XIENCE V demonstrated the following key results at two years:

• A 30 percent risk reduction in TLF compared to TAXUS (6.9 percent for XIENCE V vs. 9.9 percent for TAXUS, p-value=0.003).

• A 29 percent risk reduction in major adverse cardiac events (MACE) compared to TAXUS (7.1 percent for XIENCE V vs. 10.1 percent for TAXUS, p-value=0.003). MACE is a composite clinical measure of safety and efficacy outcomes for patients, defined as cardiac death, heart attack (myocardial infarction or MI), or ID-TLR driven by lack of blood supply.

• A 34 percent risk reduction in ID-TLR compared to TAXUS (4.5 percent for XIENCE V vs. 6.9 percent for TAXUS, p-value=0.004).

• A 25 percent risk reduction in cardiac death or target vessel MI compared to TAXUS (3.1 percent for XIENCE V vs. 4.2 percent for TAXUS, p-value=0.11).

• A 34 percent risk reduction in heart attacks attributed to the target vessel compared to TAXUS (2.3 percent for XIENCE V vs. 3.5 percent for TAXUS, p-value=0.04).

• Comparable rates in cardiac death compared to TAXUS (0.9 percent for XIENCE V vs. 1.3 percent for TAXUS, p-value=0.34).

• A 70 percent risk reduction in stent thrombosis per protocol definition compared to TAXUS (0.33 percent for XIENCE V vs. 1.25 percent for TAXUS, p-value=0.002).

• A 64 percent risk reduction in stent thrombosis per ARC definition of definite/probable stent thrombosis compared to TAXUS (0.42 percent for XIENCE V and 1.23 percent for TAXUS, p-value=0.008).

"The latest results from SPIRIT IV confirm the durable and outstanding performance of XIENCE V and demonstrate why physicians continue to embrace it for the treatment of their patients with coronary artery disease," said Charles A. Simonton, M.D., FACC, FSCAI, divisional vice president, Medical Affairs, and chief medical officer, Abbott Vascular. "In addition to strong efficacy results, the SPIRIT IV two-year data show a substantial safety advantage for XIENCE V compared to TAXUS, with very low rates of stent thrombosis."

"The two-year results for SPIRIT IV provide convincing longer-term data for XIENCE V's exceptional performance," said Robert Hance, senior vice president, vascular, Abbott. "In trial after trial, the consistently strong safety and efficacy results we see in large, simple and complex patient populations continue to confirm why XIENCE V has become the leading drug eluting stent around the world."

Event Rates in Complex Patients

The SPIRIT IV trial included multiple complex patient subgroups, including more than 1,100 patients with diabetes, who typically are sicker and have more challenging coronary artery disease. In patients with diabetes, XIENCE V demonstrated numerically lower TLF rates compared to TAXUS through two years (9.2 percent for XIENCE V vs. 10.4 percent for TAXUS, p-value=0.69). In patients without diabetes, XIENCE V demonstrated a 41 percent risk reduction in TLF compared to TAXUS through two years (5.9 percent for XIENCE V vs. 9.7 percent for TAXUS, p-value=0.0005). In the endpoint of ARC definite/probable stent thrombosis, XIENCE V demonstrated a 9 percent risk reduction compared to TAXUS in patients with diabetes (1.05 percent for XIENCE V vs. 1.28 percent for TAXUS, p-value=0.86), and a 90 percent risk reduction compared to TAXUS in patients without diabetes (0.12 percent for XIENCE V vs. 1.22 percent for TAXUS, p-value=0.0002).

In addition, XIENCE V demonstrated low event rates in analyses of multiple subgroups(3) that are frequently treated in routine clinical practice, such as patients with smaller vessels (reference vessel diameter less than or equal to 2.75 mm), patients with longer lesions (lesion length greater than 13.3 mm) and patients with multiple lesions. In patients with smaller vessels, XIENCE V demonstrated a 33 percent reduction in TLF compared to TAXUS at two years (7.3 percent for XIENCE V vs. 10.9 percent for TAXUS). In patients with longer lesions, XIENCE V demonstrated a 36 percent reduction in TLF compared to TAXUS at two years (7.2 percent for XIENCE V vs. 11.3 percent for TAXUS). In patients with two or more lesions treated, XIENCE V demonstrated a 25 percent reduction in TLF compared to TAXUS at two years (9.6 percent for XIENCE V vs. 12.8 percent for TAXUS).‹