A Medical Device Daily

There's a new entry in the multi-million-dollar pharmacologic stress agent market and an even safer participant in this testing sector, according to the company promoting the product.

CV Therapeutics (CVT; Palo Alto, California) and Astellas Pharma U.S. (Deerfield, Illinois) an affiliate of Astellas Pharma (Tokyo), reported on Friday during a conference call to investors and media that the FDA has approved Lexiscan (regadenoson) injection, an A2A adenosine receptor agonist, for use as a pharmacologic stress agent in radionuclide myocardial perfusion imaging (MPI).

As an interesting market back story to the announcement, Astellas, CVT's partner in the endeavor, produces Adenoscan, the current market leader in the pharmacologic stress agent field.

CVT originally partnered with Fujisawa Pharmaceutical, which later became Astellas, in 2000.

Under the agreement terms, CVT is responsible for managing the clinical development program, with Astellas taking over manufacturing, selling and marketing activities in North America. In addition to milestones and royalties, CVT also is reimbursed for 75% of the development costs.

Adenoscan made more than $317 million in U.S. sales last year, but it has proven to be clinically problematic because linked to serious side effects, such as second-and third-degree atrioventricular block, cardiac arrest and ventricular tachycardia.

Lexiscan, on the other hand, is more selective, hitting only the A2A-adenosine receptor, which is responsible for coronary vasodilation, according to CVT.

The agent is delivered as a rapid bolus (in about 10 seconds), with no dose adjustment required for body weight. Dose requirements are required in the use of Adenoscan and other such agents.

"All patients get the same dose to eliminate dosing errors," Chris Hogue of CVT's Commerical Business Analytics Team, said during the Friday conference call.

Only one IV is attached to the arm, as opposed to Adenoscan, which uses two. First, the Lexsican is administered, then a saline solution and finally a radio active isotope follows.

The A2A adenosine receptor is the adenosine receptor sub-type responsible for coronary vasodilation. MPI tests, commonly called cardiac stress tests, identify areas of poor blood flow in the heart to help detect and characterize coronary artery disease, the most common type of heart disease.

Many patients exercise on a treadmill to generate the increase in coronary blood flow necessary to perform an MPI study.

However, almost half of the patients undergoing the 7.5 to 9.3 million cardiac stress tests each year are unable to exercise adequately because of medical conditions. For these patients, a pharmacologic stress agent that temporarily increases blood flow through the coronary arteries is used to mimic the increase in coronary blood flow caused by exercise.

The approval of Lexiscan marks CVT's second product commercialization okay in two years.

The company introduced Ranexa (ranolazine extended-release tablets) early last year for the treatment as a second-and third-line use in chronic angina. Ranexa was licensed from an affiliate of Roche Holdings (Basel, Switzerland) in the mid-1990s.

"We took [Lexiscan] from discovery to approval in less than 10 years, which is stellar performance, and it ran through a number of trials that were successful," Louis Lange, MD, PhD, CEO and chairman of CVT said, during the call.

Lange characterized the clinical trial outcomes as "very successful" and that they had yielded "extremely" positive results.

Lexiscan, was tested in 1,500 patients in 10 clinical trials to support marketing approval.

In two identically designed, Phase III clinical trials, Lexiscan met primary endpoints for scan agreement rates by showing, with 95% confidence, that MPI studies conducted with Lexiscan were similar to MPI studies conducted with Adenoscan (adenosine injection).

Lexiscan was generally well-tolerated in both Phase III studies. The most common adverse events reported in patients who received Lexiscan were shortness of breath, headache, flushing, chest discomfort, dizziness and nausea.

CVT is focused primarily on developing molecular cardiology solutions.