In a move that takes the one step closer to having a drug-eluting stent (DES) on the U.S. market, Medtronic (Minneapolis) last month submitted its first pre-market approval (PMA) module to the FDA for the Endeavor coronary stent system, the first step toward entering the U.S. DES competition. If the company’s U.S. efforts prove successful, Medtronic would join big-name competitors Johnson & Johnson (New Brunswick, New Jersey), with its Cypher sirolimus-eluting device, and Boston Scientific (Natick, Massachusetts), with the Taxus Express2 paclitaxel-eluting system, in domestic commercialization..

The Endeavor stent, which received the CE mark in late July (Medical Device Daily, Aug. 2, 2005), is made of a cobalt alloy and has a unique modular architecture designed to enhance deliverability over standard bare-metal stents. In addition to the drug compound ABT-578, a drug compound licensed from Abbott Laboratories (Abbott Park, Illinois) the Endeavor stent is coated with phosphorylcholine, a polymer licensed from Biocompatibles International (Oxford, UK) that is designed to simulate the outside surface of a red blood cell and mimic the structure of the natural cell membrane.

Scott Ward, president of Medtronic Vascular (Santa Rosa, California), said the company has worked “diligently” with the FDA to develop a well-designed schedule of modular submissions that meet the agency’s requirements for the Endeavor stent and the new molecular entity, ABT-578. He said the modules will reflect the depth of the entire ENDEAVOR clinical trial program, including key safety data from the current ENDEAVOR IV trial. By the time the final PMA module is submitted, Medtronic will have safety and efficacy data on more than 2,000 patients implanted with the Endeavor stent.

“This is the first of four PMA modules that we will file with the FDA over the coming year,” Ward said. “We are preparing a thorough and comprehensive dossier that reflects Endeavor’s extensive pre-clinical and clinical experience. We will submit the final PMA module when we have sufficient data to support the key safety and efficacy claims for the Endeavor Drug-Eluting Coronary Stent System.” And Medtronic CFO Gary Ellis, said, “Only coronary stents remain an area where we have yet to achieve market leadership,” noted CEO Art Collins said medical technology remains “a very vibrant growth industry” as an aging population becomes more susceptible to chronic diseases.

In early October, the company also reported launch of its 8,000-patient ENDEAVOR V post-market registry, with the first patient enrollment in Austria. The trial is a multi-center study in Europe, Asia and other areas outside of the U.S. at about 200 centers. The Endeavor DES received European Commission approval in July.

Angiotech in pact with CombinatoRx

Angiotech Pharmaceuticals (Vancouver, British Columbia), the company riding high as a supplier of the drug paclitaxel to Boston Scientific for its Taxus DES, will pay nearly $42 million to CombinatoRx (Boston) to gain access to that company’s library of more than 2 million combinations of pharmaceuticals for use in a variety of potential new drug/device combinations. The deal consists of a $27 million license and research fee and a $15 million investment in CombinatoRx. In addition, CombinatoRx will receive milestone payments and royalties from Angiotech for each combination pharmaceutical compound commercialized by Angiotech or its partners.

The deal targets the area of vascular therapies – such as peripheral artery disease and coronary stenting – as well as orthopedics and generally surgery. William Hunter, MD, president and CEO of Angio-tech, said during a conference call, that access to various combination compounds held by CombinatoRx “will enhance our repurposing known drugs to treat local vascular and orthopedic disease and that may be of immediate use in certain of our key product development programs, including the treatment of restenosis in coronary stent applications.”

“We would not have done this deal if we didn’t think there were things that had a high probability of going into clinic within a 12- to 18-month time span,” said Rui Avelar, Angiotech’s senior vice-president of medical affairs communications.. “We are not expecting the return on this investment is going to be five to 10 years out ... the regulatory pathway will not be as protracted as it might be if these compounds were unknown.”

The intellectual property developed during the research collaboration will be jointly owned, but exclusively licensed to Angiotech in its fields of drug/device combinations and certain local drug delivery products and to CombinatoRx primarily for systemic therapies, and for a limited number of drug-device combination fields.

FDA keeps ‘hold’ on Hemopure trial

Biopure (Cambridge) last month hit another pothole in the regulatory road, reporting that submission of additional information by the Naval Medical Research Center (NMRC; Silver Springs, Maryland) failed to remove the FDA’s hold on its Phase IIb/III clinical trial, dubbed RESUS, of its lead product Hemopure. The company reported that for “the first time,” the FDA stated its concern with the “vasoactivity” of the product formulation. It said the agency advised it that “the only practicable path forward” for the trial is to develop a new, less-vasoactive formulation. The RESUS (Restore Effective Survival in Shock) trial proposes to use Hemopure for out-of-hospital treatment of trauma patients.

RESUS is designed as a single- blinded, multi-center, randomized trial to assess the safety and efficacy of Hemopure vs. standard treatment in reducing morbidity and mortality in injured patients experiencing hemorrhagic shock (acute blood loss) out of hospital, where blood is not available for transfusion. Patients would receive either Hemopure or standard therapy (crystalloid solution) at the scene and during transport to a hospital.

The NMRC submitted its IND to the FDA’s Center for Biologics Evaluation and Research (CBER) in June, and it was placed on hold in July. The NMRC then modified the proposed protocol and submitted a response to CBER’s clinical hold letter in September. Biopure said that CBER has maintained the “hold,” and disagreement continues regarding the risk-benefit profile and the clinical significance of potential vasoactivity associated with Hemopure.

The bad news was balanced with Biopure’s report that it has received regulatory approvals in Belgium to initiate a Phase II trial of Hemopure in coronary angioplasty patients and in South Africa to initiate a Phase II trial in patients undergoing lower limb amputation.

In Belgium, the Directorate-General for Medicinal Products has approved the company’s clinical trial application for a 20-patient, randomized Phase II trial in patients undergoing intra-coronary (IC) balloon angioplasty to support subsequent trials of Hemopure in patients experiencing a heart attack. In South Africa, the Medicines Control Council approved a protocol for a randomized, multi-center, single-blinded, parallel-group, placebo-controlled Phase II trial of Hemopure in limb ischemia patients.

Free replacement program for restenosed Taxus

In a move basically amounting to a product guarantee, Boston Scientific (Natick, Massachusetts) said that beginning in 2006 it will offer participating U.S. medical centers a Taxus Express2 DES at no additional charge if a patient requires a re-intervention due to restenosis of a previously implanted Taxus Express2. The program will run throughout 2006. Boston Sci will provide the replacement if a participating center implants a Taxus Express2 stent and the patient returns with a stent that restenoses within 12 months of implantation,

Citing the Taxus system as the global market leader among drug-eluting stent systems and noting that it has now benefited more than 1.8 million patients worldwide, Hank Kucheman, president of Boston Scientific’s Interventional Cardiology business, said the Taxus Stent Assurance Program “is our way of saying that we stand squarely and confidently behind our product.”

St. Jude eyes 2nd spot in neuromodulation

St. Jude Medical (SJM; St. Paul, Minnesota) last month said that it plans to acquire Advanced Neuromodulation Systems (ANS; Plano, Texas), a maker of implantable devices used to treat chronic pain, in a deal valued at $1.3 billion. If consummated, the deal will make it the second-largest player in the spinal chord stimulation market, an area where it previously had no market share, and place it just behind larger med-tech titan Medtronic (Minneapolis). SJM plans to pay $61.25 in a tender offer, with the deal slated for completion by year’s end.

ANS is a primary player in the estimated $1 billion neuromodulation medical device market and already holds a No. 2 market share position in the spinal cord stimulation segment behind Medtronic (Minneapolis). Neuromodulation is the delivery of very small, precise doses of electricity or drugs directly to nerve sites to treat patients suffering from chronic pain or other disabling nervous system disorders. The company also has clinical trials under way for new indications to address the expanding markets for Parkinson’s disease and essential tremor.

Daniel Starks, St. Jude President and CEO, in a conference call said that the acquisition provides his company “yet another major long-term growth platform” and an “immediate foothold in one of the fastest-growing and most exciting segments of the medical device industry where we do not already participate.” ANS, he said, will gain “a strong international presence and increased resources that we believe are necessary to fully capture the opportunities in ANS’s market.” About 40% of SJM’s revenues come from sales outside the U.S., while less than 10% of ANS revenues come from international sales. ANS products are sold in about 30 countries while SJM has a presence in more than 130 countries.

Starks said that the synergy produced by the deals will be the result of “technology crossover in microelectronics, batteries leads and programmers [that] will benefit the flow of electronics both in neuromodulation and cardiac rhythm management. Chris Chavez, ANS president and CEO, emphasized that the combination is less a consolidation than an acceleration of ANS activities “by bringing new resources to help us tap our incredible market opportunities.” He noted that “there is virtually no overlap in the markets served by St. Jude Medical and ANS today, but our technologies are extremely complementary.”

ANS will become a newly created division of St. Jude Medical. The bulk of that company’s existing executive management team is expected to remain with the combined company, including Chavez, who will become the president of the ANS division, which will remain headquartered in Plano.

ANS was itself a would-be acquirer in September 2004 but was spurned in its efforts to buy Cyberonics (Houston) in a transaction valued at the time at nearly $525 million. It had acquired a 14% stake in that company the previous month. Cyberonics is focused on vagus nerve stimulation therapy, an implantable strategy different than that of ANS. But the stake held by ANS could make it a beneficiary of the St. Jude acquisition.

AngioSculpt gets infrapopliteal PAD approval

The FDA has given 510(k) clearance to AngioScore (Alameda, California) to market its AngioSculpt Scoring Balloon Catheter for the treatment of infrapopliteal peripheral arterial disease. The company said the AngioSculpt joins a new class of specialty medical devices aimed at treating peripheral arterial disease (PAD), which it termed one of the fastest-growing segments in the worldwide interventional marketplace. An estimated 10 million patients suffer from PAD in the U.S. alone, of whom only about 800,000 undergo a revascularization or amputation procedure each year.

AngioScore said the AngioSculpt family of devices for PAD has the potential to “favorably improve the clinical outcomes” of a large portion of these patients. CEO Thomas Trotter said, “We believe that the AngioSculpt represents a major advancement in the state of the art, and will provide physicians worldwide with an outstanding new medical device for use in the treatment of PAD.” He said distribution is slated to begin in 1Q06.

Trotter said he expects the infrapopliteal PAD indication to be only the first in a series of applications for the global interventional market.