MUNICH, Germany — Restenosis, the reclosing of arteries opened after surgery interventions, continues to plague the plaque-busting vascular intervention techniques, defying even state-of-the-art drug-eluting stents (DES).

In September a team of German engineers won the CE mark for what they believe is the ultimate device that can win this long struggle, a nuclear weapon to destroy the DNA structure of cells that start growing within minutes after a balloon reopens a clogged vessel.

The maker of the device, ITM FlowMedical (Garching, Germany), said it expects to close contracts with up to seven German hospitals to begin vascular brachytherapy (VBT) procedures in late November.

A sales staff of four in October began working the countries of the Benelux, Scandinavia and UK. The company also said it is negotiating with potential partners in Russia, Turkey and Brazil where the CE mark facilitates a national approval.

And FlowMedical's chief executive, Hartmut Scheurer told Medical Device Daily, "We expect to begin our development of activities for the United States market in mid-2009," adding that he expected a 510(k) approval to take from 12 to 18 months.

Radiation of cells in the artery targeted for a percutaneous transluminal angioplasty (PTA) is not a new procedure.

Endovascular brachytherapy (EVBT) was actually an early casualty of the stunning DES conquest of the cardiac intervention market.

As Michael Simonsen noted in Biomedical Business & Technology in May 2002, "The market for intravascular brachytherapy products emerged as a major segment in 2001, with worldwide sales exceeding $90 million in the first full year. The future of that segment is uncertain, however, since drug-eluting stents now also are showing promise for treatment of in-stent restenosis."

By 2005, vascular brachytherapy was finished with DES established as the gold standard.

The two companies that led the field with irradiated cardiac intervention devices are no more.

In March 2004, Guidant (Indianapolis) discontinued its Galileo Intravascular Radiotherapy System "due to the significant competitive impact of drug-eluting stents," and the company subsequently was sold to Boston Scientific (Natick, Massachusetts).

The second brachytherapy device maker, Novoste (Norcross, Georgia), ran out of money in 2004 since no one wanted to back the fight against the increasingly profitable DES competition.

Novoste's VBT business was turned over to Best Vascular (Springfield, Virginia), a developer of radiation seed products, which agreed to assume the liabilities (Medical Device Daily, Oct. 14, 2005)

FlowMedical is undaunted and plans a flanking maneuver against DES by focusing on the fast-growing peripheral intervention market with a new generation design that solves several challenges for using radioactive materials in an operating theater.

"In the peripheral market, we have a unique selling proposition," said Scheurer. "Stenting arteries is not often viable and usually medically not relevant following peripheral angioplasties to keep the vessel open. The only effective therapy in this market will be our device."

He noted that the number of lower leg interventions is increasing tremendously due to interventionalists applying skills acquired in coronary angioplasties.

"Three years ago interventionalists has no balloons to treat the lower leg vessels but today they have learned to apply balloons developed for cardiac procedures as the vessel size is similar, " Scheurer explained.

The company's name derives from its innovative approach for flowing a radioactive liquid into a balloon catheter.

The isotope in the liquid, Rhenium-188, also is new and improved, emitting a tightly focused beta radiation with rays extending only 2.5 mm, rather than the long and unmanageable gamma-emitting isotopes used in the first generation devices.

Rhenium has a half-life of 17 hours, which means that after 170 hours it is an inert solution that can be discarded with hospital trash. The gamma isotopes used previously had a half-life of 30 years and continued to decay over 300 years.

Rhenium-188, approved as a Class IIB medical device under the CE mark, is derived from a tungsten isotope FlowMedical purchases from a Russian nuclear reactor that is placed in a generator developed by Isotopen Technologien M nchen (ITM).

By placing the generator, about the size of a garbage can, with nuclear medicine labs near the cath lab where a rhenium- PTA will be performed, the isotope can be created on demand and in an unlimited supply, another challenge faced by the first generation technology.

A single vial of the rhenium liquid is good for five procedures the same day before it decays and becomes ineffective.

Solving a third challenge, FlowMedical designed an application system kit (ASK) that can be wheeled into a cath lab on a mobile cart thanks to a tungsten housing shielding the isotope emissions, where earlier technologies required patients to be moved to a nuclear medicine facility.

The isotope and special kit were developed by engineers at Technical University of Munich in Garching, a short walk from the offices of FlowMedical and ITM, which are in a business incubator built around a nuclear reactor used for research.

In this procedure, the vascular interventionalist first dilates a balloon in the targeted artery, and then attaches the catheter to the Rhenium-188 ASK. Using plunger mechanism on the tungsten-shielded ASK, the liquid carrying the isotope is drawn from the vial into a syringe and then sent through the catheter to the balloon in the targeted vessel segment.

Filling the balloon, the rhenium rays penetrate the vessel walls evenly to the 2.5 mm depth, sufficient to affect the muscle and fiber cells of the thickest layer, the tunica media. It these cells that, reacting to the violence of the balloon dilation will begin growing within minutes after the PTA intervention.

The exposure time varied from three to seven minutes with the liquid pulsed in and out of the balloon to assure blood flow during the procedure. Dosimetery calculations for rhenium-188 are being developed by a medical team at the Zentrum Klinikum Augsburg (Augsburg, Germany) whose doctors were the original impetus for ITM to develop the isotope, according to Scheurer.

Having solved the technical issues, ITM brought Scheurer onboard to to bring the Rhenium-PTA device to market.

A former chief executive and shareholder with Bavaria Medizin Technologie (Oberpfaffenhofen), a contract manufacturer of cardiac catheters for Abbott Laboratories (Abbot Park, Illinois), Scheurer earlier in his career ran the 4 billion Knorr Bremse (Munich), a maker of braking systems for heavy rolling stock.

Scheurer said the starting point is effectiveness of the treatment. Before the EVBT technology lost the commercial fight against DES, more than 150,000 interventions were performed with clinical studies showing solid results against restenosis, he said.

In its proof of concept for regulatory approval in Germany, where the procedure is reimbursed, FlowMedical showed that at 16 months the 22 patients treated at the Augsburg hospital experienced restenosis at the rate of 13.6%

"There is no comparison for stents in peripheral procedures, but looking at DES results in cardiac procedures, which are 16% at six months and 20% at 18 months, we are clearly doing better," said Scheurer, who added that the average patient age at the Augsburg clinic is 75 years and they present with multiple morbidities.

Key opinion leaders who have agreed to work with the Rhenium-PTA from FlowMedical are Erich Minar, MD, at the University of Vienna Medical School (Vienna, Austria), who published a series of clinical studies based on the first-generation technology from Novoste, and Judah Weinberger, MD, with the Interventional Cardiology Center of Columbia-Presbyterian Medical Center (New York).

"Dr. Weinberger told us last year at the American Heart Association meeting that he wanted to work with this device once it received a CE mark, which we now have, so he is now arranging a special permission to bring the device to New York," Scheurer said.

There were 800,000 peripheral artery interventions in the U.S. in 2007, according to Scheurer, who calculates that at an average $2,500 per intervention a 10% market share would represent a $200 million business.

FlowMedical is seeking a joint venture partner with an existing sales structure for the U.S., he said.

Asked if he welcomed an acquisition of the company, he smiled and said, "That is our exit strategy."

Schreurer has a 10% stake in FlowMedical, whose other shareholders are the Chairman Udo Vetter of Vetter Pharma-Fertigung (Ravensburg, Germany), a developer and manufacturer of aseptically pre-filled application systems, such as syringes, for pharmaceutical and biotechnology companies, and Oliver Buck, scion of a Bavarian family with deep roots in manufacturing.