The race to develop and commercialize a second-generation drug-eluting stent (DES) is poised to heat up in the second half of this year. Johnson & Johnson (New Brunswick, New Jersey), while initially appearing to be a contender in this particular derby, fell far back in the pack this past month with the failure of one of the more innovative products to reach key trial endpoints.

The failure was that of the Costar DES, under development by Conor Medsystems (Menlo Park, California), recently acquired by J&J. J&J's $1.4 billion purchase of Conor in February clearly was an attempt to bolster its offerings in the sector — or, rather, offering, the Cypher stent made by J&J subsidiary Cordis (Miami Lakes, Florida).

Citing issues related to what it suggested was a sub-optimal dosing of the drug paclitaxel, Conor reported that its pivotal CObalt Chromium STent with Antiproliferative for Restenosis (COSTAR II) trial for the CoStar DES failed to meet its primary endpoint of non-inferiority to the major competitor to the Cypher, Boston Scientific's (Natick, Massachusetts) Taxus Express 2 stent with respect to major adverse cardiac events (MACE) in patients with multi-vessel or single-vessel disease.

With the trial results, Conor said it would immediately terminate ongoing clinical trials for the CoStar stent and will not attempt to file its premarket approval application with the FDA. Additionally, the company discontinued sales of the CoStar through its partners in certain countries in Europe, Asia and Latin America where the CoStar stent is already approved. It said it will work with those partners to facilitate return of product in inventory in customer accounts.

In a conference call, Campbell Rogers, MD, chief technology officer, cardiovascular franchise for Conor, said the eight-month MACE rate for the CoStar DES was 11% vs. 6.9% for the Taxus, which also elutes paclitaxel. "This difference did not meet the pre-specified definition of non-inferiority for the CoStar stent," Rogers said.

The company also failed to achieve non-inferiority for in-stent late loss (0.48mm for CoStar vs. 0.15mm for Taxus). Additionally, target vessel revascularization was 8.1% for CoStar vs. 4.3% for Taxus, with CoStar demostrating six thrombotic events (five within 30 days, one beyond 30 days) vs. one for Taxus (0 within 30 days). Rogers said the company was attributing the trial failure to the "very low doses of [paclitaxel] that were chosen to be delivered by the CoStar stent."

Conor said it will continue to develop another stent using its unique design — an architecture that includes hundreds of small holes to deliver the drug — but will use sirolimus, the drug employed in J&J's Cypher. Conor has bannered the architecture of the Costar as an improvement in the stent's ability to elute a drug, and perhaps as a way to avoid the problems seen in other DES products.

While expressing disappointment at the result of the trial, Nicholas Valeriani, worldwide chairman, Medical Devices and Diagnostics, for J&J, said during the call that his company is still excited about Conor's technology and its future prospects. "This was an investment in the long term, and we continue to have great enthusiasm for the promise of this stent platform in combination with the work that we've done at Cordis to create what we think will be truly the next generation of drug-eluting stents for patients with coronary disease."

Rick Anderson, J&J's company group chairman and worldwide cardiovascular franchise leader, said, "Going forward, our clinical program will be heavily focused on the study of sirolimus on the platform, as well as on investigating the vast library of therapeutic agents accessible to our scientists through the research and development programs of pharmaceutical companies in the Johnson & Johnson family of companies."

Analysts said the primary impact will be the company's inability to launch a new product in a timely fashion, giving competitors a leg up. Rick Wise of Bear Stearns (New York) wrote in a research note that because of the FDA's concerns regarding DES and the likely repercussions for new stent approvals, "this could push a Costar launch out three to four years, possibly in the 2010/2011 timeframe." He said he expects Abbott Laboratories (Abbott Park, Illinois), Boston Scientific and Medtronic (Minneapolis) to benefit — in that order — from the delay.

Good/bad news mix for Thoratec concerning HeartMate II trial

Thoratec (Pleasanton, California), a maker of products to support the failing heart, recently decided to offer up the good news first, stick the not-so-good news in the middle, and then end with some better news.

First, the positive: Thoratec reported 1Q07 revenues increased 18% over revenues in the first quarter of last year. For the quarter ended March 31, revenues were $57.3 million compared with revenues of $48.8 million in 1Q06.

Along with that news, however, came new regulatory concerns involving data interpretation of its HeartMate II trial of the company's HeartMate ventricular assist device. Thoratec said its 100-day meeting with the FDA related to its PMA filing for Bridge-to-Transplantation (BTT) approval, following the receipt of a letter that outlined a number of deficiencies in the submission. The company termed the discussion "constructive" and said that it has "an understanding of the means needed to address the issues outlined by the FDA."

The main hold-up appears to be over how to categorize patients who voluntarily remove themselves from the transplant list.

During a conference call Gary Burbach, president/CEO of Thoratec, said there were "a relatively small number of patients included in our primary cohort as successes who either voluntarily took themselves off the transplant list or were removed due to lifestyle changes or temporary changes in their health after 180 days for reasons unrelated to the device."

Burbach also said that all of the patients in question had been supported by the device for between 330 and 681 days as of mid-March and continue to do "very well" from a health and quality-of-life status. "Given the length of support and their experience on the device, we actually consider these to be some of our most successful patients," he said.

Thoratec followed all of this with better news — FDA approval of an investigational device exemption (IDE) supplement that allows the company to enroll up to 60 more patients in the BTT arm of the HeartMate II trial under a Continued Access Protocol (CAP). This is the third CAP the company has received for this trial, and the company said it recently received CAP approval for the Destination Therapy (DT) arm of the trial.

The original trial design for the BTT arm called for enrollment of 133 patients. As of April 27, the company reported that it had enrolled 296 patients in the BTT arm of the study and 188 patients in the randomized arm of the trial. The original DT trial design called for enrollment of 200 randomized patients. Total, Burbach said the company has enrolled 616 patients in the pivotal trial.

Data released from the BTT arm of the HeartMate II trial at this year's scientific sessions of the American College of Cardiology (ACC; Washington) suggested the device provides mechanical circulatory BTT support for heart failure patients and that these patients experience a lower number of adverse events and an improved quality of life while being supported by the device.

The trial enrolled 133 patients at 26 centers from March 2005 through May 2006, and the data reflected follow-up through the end of December 2006. Leslie Miller, MD, of Washington Hospital Medical Center/Georgetown University (Washington), reported that 100 patients, or 75% of the cohort, met the trial's primary endpoint, which was cardiac transplantation or survival at 180 days while remaining eligible for transplantation. The 25% (33) who did not meet the primary endpoint included 25 who died being supported on the device.

Abbott recalls Architect STAT diagnostic test for Troponin-I

Abbott Laboratories (Abbott Park, Illinois) reported that it has initiated a voluntary, nationwide recall of its Architect STAT Troponin-I diagnostic test. The product was distributed to clinical laboratories in the U.S. and internationally and is used to aid in the diagnosis of injury to heart muscle and/or heart attack.

Normally levels of Troponin, a protein found in muscle, are very low; even slight elevations can indicate some degree of damage to the heart. Abbott initiated this voluntary recall of the product after receiving what it said were a "small number of complaints" related to inconsistent or invalid test results at very low levels of Troponin-I (i.e., less than 0.1 ng/mL).

A negative test result at these levels could indicate that a person has not had heart muscle injury or heart attack, when in fact they may have for some patients. At higher levels most commonly used for making clinical decisions and evaluating patient results (i.e., 0.1 ng/mL and 0.3 ng/mL), the product continues to work as described in the product labeling.

No patient injuries have been reported. Laboratories may continue to use the product with the updated directions for use, which Abbott is distributing to clinical labs.

The additional instructions provide that: (a) for laboratories or physicians using 0.1 ng/mL or less than 0.1 ng/mL as the cut-off, samples should be retested and/or serial negative blood draws over time should be evaluated before patients are classified as negative for a heart attack; (b) recent negative results less than 0.1 ng/mL should also be re-evaluated and the ordering physicians should be notified; (c) laboratory reports of negative patient results less than 0.1 ng/mL should contain the cautionary language contained in (a) and (b) above.

Abbott previously issued a product correction notice to customers explaining the issue and advising them to evaluate and adjust the reference ranges used in their laboratory when running this test. The company said it has identified the root cause and is working on correcting the issue. It has reported the action to the FDA.

Edwards Lifesciences files infringement lawsuit vs. Corevalve

Edwards Lifesciences (Irvine, California), which focuses on the science of heart valves, reported that its subsidiary, Edwards Lifesciences PVT, has filed a patent infringement lawsuit against CoreValve (also Irvine) in the District Court of Dusseldorf, Germany. The suit seeks relief for alleged infringement of a patent for transcatheter heart valve technology.

"We are committed to protecting our valuable intellectual property as well as the interests of our clinician-inventors who partner with us to transform patient care for people with advanced cardiovascular disease," said Michael Mussallem, Edwards' CEO and chairman.

Edwards said it has "opened discussions" with CoreValve on a possible licensing arrangement.

The relevant patent, EP 0 592 410 B1, is co-owned by Dr. Henning Rud Andersen of Aarhus, Denmark, and his colleagues, who licensed it in 1993 to Heartport (Redwood City, California), now a subsidiary of Johnson & Johnson (New Brunswick, New Jersey). Edwards has an exclusive sublicense to the Andersen patent, which relates to a valve prosthesis for implantation by means of a catheter, and the product named in the suit is the CoreValve ReValving system

Endovasc launches BioFlow; Channel Group forms Lesanne Life Sciences

CDU this month introduces a new feature — new ventures in the cardiovascular field:

• Endovasc (Montgomery, Texas) reported the creation of BioFlow as a new, wholly owned subsidiary, to manage the continued development of biodegradable stents. Endovasc and Nathan Blumberg, MD, have jointly transferred the intellectual property from both of the previous joint ventures involving TissueGen (Arlington, Texas) into BioFlow.

Diane Dottavio, PhD, president/CEO of Endovasc, told CDU that the first project of BioFlow would be to develop a biodegradable urinary stent for ureteral application. Dottavio said that urinary stents are currently made of rubber or silicone and are not biodegradable. After a procedure such as ureteroscopies (procedures to visualize the ureter and extract stones) and lithotripsies (external ultrasonic destruction of stones), a stent is often placed in the urinary tract to prevent the small stone fragments from coalescing and obstructing the ureter after the procedure.

"Once the fragments are gone they have to remove the stent, which is a second whole procedure, it's painful, and it produces a cost to the patient that we think we can eliminate," Dottavio said.

BioFlow will manage product definition and the development process through a sponsored laboratory research agreement. The objective is to develop biodegradable ureteral and urethral stents that can be degraded in the body within seven to 14 days after a procedure, Dottavio said, compared to other biodegradable stents on the market which degrade in more like six weeks, she added. All IP developed under this research agreement is assigned to BioFlow.

Endovasc reported partnering with TissueGen in 2003 to develoop a bioreabsorbable drug-eluting stent so that after the drug is gone from the stent, the stent is reabsorbed by the body.

Endovasc is focused on developing and commercializing drug candidates in the areas of cardiovascular and metabolic medicine. Endovasc is organized as a business development company, and owns interests in three portfolio companies:

• The Channel Group (New York) said it has formed Lesanne Life Sciences (Ivoryton, Connecticut), a diagnostic company developing a simple blood test to detect the occurrence of a stroke.

Lesanne said that its diagnostic test is designed to detect low levels of a protein biomarker present only in the brain and related central nervous system tissue of healthy individuals.

In a pilot clinical trial, the biomarker was present in blood samples obtained from stroke patients, but was not found in control patients. Pre-clinical experiments showed that the biomarker was detectable readily within 15 minutes of induction of a stroke in animal models. The company said that these findings imply that it might be possible for emergency personnel and physicians to confirm the occurrence of stroke, even before a patient is subjected to imaging.

The company is developing both a qualitative blood test to be used in emergency settings for diagnosing a stroke and a quantitative blood test to be used in the hospital to monitor recovery from a stroke.

The company also plans to extend the use of its biomarker as a diagnostic for neurological ischemia associated with traumatic brain injury (TBI) and various medical procedures, including coronary artery bypass graft (CABG) surgery, cardiac surgery, and coronary angiography and angioplasty.

Lesanne's founders are Robert Beckman, Allan Goldberg, PhD, Philip Sussman, Ann Cornell-Bell, PhD, and Leslie Riblet, PhD.