Replies to post #81215 on Biotech Values

[DewDiligence]

Re: DES market shares

I think the numbers look right. I do not think ABT will give the exact Xience numbers until the co-marketing agreement with BSX is over.

That’s correct—ABT doesn’t want anyone to know how much BSX pays ABT for Promus, and hence ABT lumps this amount (as well as the royalties MDT pays ABT for zotarolimus) into an aggregate sales figure for ABT’s stent business. When the Promus co-marketing deal expires (when does this happen?), ABT may be willing to break out the Xience sales and the zotarolimus royalties (which are presumably small).

After listening to the BSX call today, I think more then ever BSX will be focusing on the Promus franchise going forward. Taxus may lose share faster then I originally thought.

Agreed—the DES battle has been fought and won by Xience/Promus; BSX could soon find itself in deep doo-doo.

If Guidant could have gotten their company in order they would be sitting pretty today. ABT made one hell of a great deal!

Those are two major understatements! ABT’s Xience deal was probably the biggest coup in the history of medical devices and one of the two or three biggest coups in the history of the healthcare industry. And they didn’t even have to outbid anyone of consequence!

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MDT pays ABT $400M to settle all stent-related litigation:

http://finance.yahoo.com/news/Medtronic-and-Abbott-bw-832683289.html?x=0&.v=1

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Xience Continues to Best Taxus in Head-to-Head Competition

[This comparison could hardly be simpler: no matter how you slice it, Xience is just better (and the worldwide sales numbers reflect this: #msg-39762286). This PR contains 3-year data. “Late thrombosis,” the issue that caused the drug-eluting-stent market to go into a tailspin a few years ago, was all but non-existent in the Xience arm.]

http://finance.yahoo.com/news/Abbotts-XIENCE-VR-Continues-prnews-326186897.html?x=0&.v=1

›Abbott's XIENCE V Continues to Outperform TAXUS With Sustained Clinical Advantages and Impressive Long-Term Safety Results in SPIRIT III Trial

- Market-Leading XIENCE V Demonstrates Single-Digit Rate of Major Adverse Cardiac Events (MACE) at Three Years and a 43 Percent Reduction vs. TAXUS

- No Additional Stent Thrombosis between Two and Three Years, and Impressive Low Rate of Very Late Stent Thrombosis for XIENCE V

Monday September 21, 2009, 11:00 am EDT

SAN FRANCISCO, Sept. 21 /PRNewswire-FirstCall/ -- Long-term data presented today from the SPIRIT III pivotal U.S. clinical trial demonstrated that the observed clinical advantages of Abbott's market-leading XIENCE V® Everolimus Eluting Coronary Stent System continued to increase as compared to the TAXUS® Express2 Paclitaxel-Eluting Coronary Stent System (TAXUS). At three years, XIENCE V demonstrated a 43 percent reduction in the risk of major adverse cardiac events (MACE) compared to TAXUS (9.1 percent for XIENCE V vs. 15.7 percent for TAXUS, p-value=0.003). MACE is an important composite clinical measure of safety and efficacy outcomes for patients, defined as cardiac death, heart attack (myocardial infarction or MI), or ischemia-driven target lesion revascularization (ID-TLR driven by lack of blood supply). The three-year results from the SPIRIT III trial will be presented today by Gregg W. Stone, M.D., professor of medicine at Columbia University Medical Center, during the 2009 Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco.

"The SPIRIT III results clearly demonstrate that at three years, patients continue to benefit from having been treated with the XIENCE V stent rather than the TAXUS stent, with fewer repeat cardiac procedures and fewer heart attacks in patients who received XIENCE V," said Dr. Stone, who is also immediate past chairman of the Cardiovascular Research Foundation, New York; and principal investigator of the SPIRIT III trial.

XIENCE V demonstrated an impressive low rate of very late stent thrombosis (one to three years) with no additional events between two and three years. Per protocol, XIENCE V demonstrated a 0.2 percent very late stent thrombosis rate compared to 1.0 percent for TAXUS (p-value=0.10) at three years. Per Academic Research Consortium (ARC) definition of definite/probable stent thrombosis, the rate of very late stent thrombosis at three years was 0.3 percent for XIENCE V and 1.0 percent for TAXUS (p-value=0.34). The ARC definitions of stent thrombosis were developed to eliminate variability in the definitions across various drug eluting stent trials.

Key Results from SPIRIT III

In the 1,002-patient SPIRIT III trial, XIENCE V demonstrated the following key results out to three years:

A 43 percent reduction in the risk of MACE compared to TAXUS (9.1 percent for XIENCE V vs. 15.7 percent for TAXUS, p-value=0.003).

A 43 percent reduction in the risk of Target Lesion Failure (TLF) compared to TAXUS (8.3 percent for XIENCE V vs. 14.4 percent for TAXUS, p-value=0.005). TLF is a composite measure of important efficacy and safety outcomes for patients, defined as cardiac death, target vessel MI and TLR.

A 30 percent reduction in the risk of Target Vessel Failure (TVF) compared to TAXUS (13.5 percent for XIENCE V vs. 19.2 percent for TAXUS, p-value=0.03). TVF is a composite clinical measure of safety and efficacy outcomes defined as cardiac death, MI or ischemia-driven target vessel revascularization (TVR).

A 42 percent reduction in the risk of heart attacks (MI) compared to TAXUS (3.7 percent for XIENCE V vs. 6.3 percent for TAXUS, p-value=0.07).

A 39 percent reduction in the risk of ID-TLR compared to TAXUS (5.4 percent for XIENCE V vs. 8.9 percent for TAXUS, p-value=0.05).

Per protocol definition, a 0.2 percent rate of very late stent thrombosis compared to 1.0 percent for TAXUS (p-value=0.10). Per ARC definition of definite/probable stent thrombosis, the rate of very late stent thrombosis was 0.3 percent for XIENCE V and 1.0 percent for TAXUS (p-value=0.34).

Consistent Results in SPIRIT III Subgroup Analyses

In addition to the positive three-year results for the overall study presentation, subgroup analyses from the SPIRIT III trial demonstrated evidence of the strong performance by XIENCE V in a variety of patients and lesion types that represent complex patients. In patients with diabetes, the analysis showed there was no difference at three years in MACE between XIENCE V and TAXUS (11.0 percent for XIENCE V vs. 10.3 percent in TAXUS) . In fact, XIENCE V maintained a consistent rate of clinical events after the first year (8.7 percent MACE at one year and 11.0 percent MACE at three years), whereas TAXUS demonstrated a sustained upward trend in clinical events from one year to three years (4.7 percent MACE at one year and 10.3 percent MACE at three years). In patients without diabetes, the MACE rate for TAXUS at three years was more than double the MACE rate for XIENCE V at three years (9.1 percent for XIENCE V vs. 18.7 percent for TAXUS).

"The SPIRIT III data clearly show that XIENCE V performs in a consistent manner, with clinical benefits continuing to improve over time compared to TAXUS," said Robert Hance, senior vice president, vascular, Abbott. "We are pleased to begin this year's TCT conference with a strong showing of data for Abbott's market-leading XIENCE V, and look forward to presenting the highly anticipated SPIRIT IV one-year results later this week, which should provide physicians with additional valuable insights."

One-year results from the company's SPIRIT IV trial will be presented on Wednesday, Sept. 23, during the first late-breaking clinical trials session of the TCT conference. The SPIRIT IV trial is one of the largest randomized clinical trials between two drug eluting stents, with 3,690 patients enrolled, including more than 1,000 patients with diabetes. The study results will provide valuable information about the efficacy and safety of XIENCE V compared to TAXUS. The SPIRIT III trial was not designed to analyze statistical differences in any of the patient subgroups, as the sample sizes were too small to draw firm conclusions.

About the SPIRIT III Trial

SPIRIT III is a prospective, multi-center, randomized, single-blind, controlled clinical trial comparing XIENCE V to TAXUS in 1,002 patients (669 XIENCE V patients, 333 TAXUS patients) with either one or two de novo coronary artery lesions. The trial was conducted across 65 academic and community-based centers in the United States between June 22, 2005, and March 15, 2006.

[As previously reported]: The primary endpoint of the SPIRIT III trial was in-segment late loss at eight months, wherein XIENCE V demonstrated superiority to TAXUS with a statistically superior 50 percent reduction in late loss (mean, 0.14 mm for XIENCE V vs. 0.28 mm for TAXUS, p-value =0.004). In-segment late loss is a measure of vessel re-narrowing.

About XIENCE V

XIENCE V is used to treat coronary artery disease by propping open a narrowed or blocked artery and releasing the drug, everolimus, in a controlled manner to prevent the artery from becoming blocked again following a stent procedure. XIENCE V is built upon Abbott's market-leading bare metal stent, the MULTI-LINK VISION(®) Coronary Stent System. The VISION platform is designed to facilitate ease of delivery, making it easier for physicians to maneuver the stent and treat the diseased portion of the artery.

The XIENCE V stent is available on both over-the-wire (OTW) and rapid exchange (RX) delivery systems. Rapid exchange is the most widely used type of delivery system because it provides physicians additional flexibility to work as single operators during stent procedures.

Abbott's market-leading XIENCE V drug eluting stent is commercially available in the United States, Europe and other international markets. XIENCE V is an investigational device in Japan and is currently under review by Japan's Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency.

Abbott also supplies a private-label version of XIENCE V to Boston Scientific called the PROMUS(®) Everolimus-Eluting Coronary Stent System. PROMUS is designed and manufactured by Abbott and supplied to Boston Scientific as part of a distribution agreement between the two companies.

Everolimus, developed by Novartis Pharma AG, is a proliferation signal inhibitor, or mTOR inhibitor, licensed to Abbott by Novartis for use on its drug eluting stents. Everolimus has been shown to inhibit in-stent neointimal growth in the coronary vessels following stent implantation, due to its antiproliferative properties.

XIENCE V is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (lesions less than or equal to 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm. Additional information about XIENCE V, including important safety information, is available online at www.xiencev.com or www.abbottvascular.com/en_US/content/document/eIFU_XienceV.pdf.<

[DewDiligence]

More on Xience vs Taxus from TCT 2009



In addition to 3-year follow-up from the pivotal SPIRIT III study (#msg-41731638) and the first head-to-head data showing Xience outperformed Taxus Liberté (#msg-41855797), ABT reported data at TCT from the SPIRIT IV trial, which was a large (almost 4,000 patients) “real world” head-to-head study of Xience vs Taxus.

Real world in this context means that patients in SPIRIT IV did not have angiographic follow-up for asymptomatic conditions, as they did in the pivotal SPIRIT III study. Thus, instead of the SPIRIT III primary endpoint of late loss (which obviously requires angiographic follow-up), the primary endpoint in SPIRIT IV was Target Lesion Failure (TLF) at one year. TLF was defined as a composite of cardiac death, MI in the target vessel, and revascularization of the target vessel. (TLF is thus more specific to the target lesion than the usual MACE endpoint used in PCI studies, which includes non-fatal MI’s regardless of the triggering locations.)

The image above shows the SPIRIT IV Kaplan-Meier curves for the TLF primary endpoint. The HR was a stellar 0.61 and the p-value was 0.0008.

Source: http://www.xiencev.com/documents/spirit_iv_1year.pdf

[DewDiligence]

ABT’s Xience stent approved in Japan:

http://finance.yahoo.com/news/Abbotts-XIENCE-VR-Approved-in-prnews-3859294386.html?x=0&.v=1

Japan is the world’s second-largest market for drug-eluting stents and was the only remaining major market in which Xience was not yet approved.

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Cypher Tops Endeavor With Ease in Danish Study

[MDT’s Endeavor stent has held a distant fourth-place ranking among DES’s in all major jurisdiction (#msg-39762286), and this new study surely won’t help. The original premise for Endeavor—that modest efficacy in terms of late loss was outweighed by superior safety—now appears to be flawed.

The larger question is whether this new information is even material from a commercial standpoint. While Endeavor has been an also-ran from day one, Cypher, once the market leader, is steadily losing market share to the clearly superior Xience platform from ABT. JNJ’s hopes to become a significant player in drug-eluting stent would seem to rest on the Nevo platform. ]

http://www.reuters.com/article/idCNN1513785620100315

›Mon Mar 15, 2010 11:12am EDT
By Bill Berkrot and Debra Sherman

* Fewer major adverse events seen with J&J stent

* 4.5 pct event rate with Cypher vs 9.7 for Endeavor

* Medtronic critical of data, trial design

ATLANTA, March 15 (Reuters) - Johnson & Johnson's <JNJ.N> Cypher drug-coated stent led to significantly fewer heart attacks, deaths and need for repeat procedures than Medtronic Inc's <MDT.N> newer Endeavor stent using a different drug, according to a head-to-head study conducted by Danish researchers.

Eighteen months after the stents were placed, 9.7 percent of Endeavor patients suffered cardiac death, heart attacks or target vessel revascularizations compared with 4.5 percent of those who received J&J's Cypher, according to data presented at the American College of Cardiology scientific meeting in Atlanta.

Medtronic questioned the data and study's design, calling it biased toward Cypher. [Nice try, but see next sentence.] The study was supported by grants from both companies.

…Based on findings from a previous clinical trial of Endeavor, researchers said they believed the Medtronic stent would prove superior and provide strong protection against blood clots in the stented area and heart attacks.

"But we found there is a high risk of early stent thrombosis and early heart attack in the Endeavor," said Dr. Michael Maeng, lead researcher of the 2,332-patient study, from Aarhus University Hospital in Denmark.

Maeng speculated that the higher number of adverse events seen with Endeavor may have been related to faster delivery of the drug coating the device.

Cypher, the first drug eluting stent to reach the market, is coated with a medicine called sirolimus. Endeavor, the fourth entry into the increasingly competitive sector, is coated with zotarolimus.

"If you have to compare the two stents, the Cypher stent is a better stent," Maeng said.

Medtronic took exception to the results and issued a lengthy press release attempting to refute the data.

The study "uses an unconventional methodology, which raises questions about the reproducibility, viability and applicability of the results," Medtronic spokesman Joe McGrath said in a statement.

Maeng argued that his study was more meaningful as it was carried out in a real world setting on a variety of patients with coronary artery disease. The Danish study also included more than five times as many patients as the Endeavor trial cited by Medtronic in its defense.

"The Endeavor III trial was performed on 436 low-risk patients with a single non-complex lesion," Maeng said.

"If you want to assess clinically relevant differences between the various drug-eluting stents, you have to compare the stents in routine clinical care patients," Maeng said.

However, Medtronic's McGrath said the Danish study "produced unexpectedly low event rates and inconsistent data for the Cypher stent compared to nearly every other trial in which the device has been evaluated."‹