Mosaic Heart Valve Approved With Two Post-Market Study Requirements

Medtronic will need to conduct two postmarket studies on the Mosaic porcine bioprosthesis heart valve, FDA explains in its approval letter.

In one, the firm will be required to follow for six years the 500 aortic valve replacement (AVR) and 200 mitral valve replacement (MVR) patients enrolled in the clinical trials used to support the PMA. That study will be complete when 100 AVR and MVR patients have attained a six-year evaluation.

In addition, Medtronic will need to monitor newly implanted U.S. patients for valve-related events resulting in death, re-operation or explant. The study should be designed to identify the major failure modes of the device and establish their frequency, according to the agency. In particular, the firm should determine the likelihood of an event rate of structural deterioration.

Medtronic must submit protocols for both studies to FDA by mid-September for review by the agency. Final results of the studies must be reflected in the firm's annual report and in labeling when they are completed, the agency notes.

Originally submitted in October 1999 and amended in November, April and July, the Mosaic PMA was approved July 14 for the replacement of malfunctioning native or prosthetic aortic and mitral heart valves. Approximately 90,000 such valves are implanted annually in the U.S.

The reduced-profile Mosaic, which has been available in Europe since 1997, incorporates a flexible stent, the firm notes. The stents of both models are constructed from acetal homopolymer and covered with polyester fabric.

The device is similar to Medtronic's Hancock II tissue valve for replacement of pathologic or prosthetic aortic and mitral valves. Approved in October, the tri-leaflet porcine valve is fabricated such that the right coronary cusp and its flow-impeding muscle shelf are replaced with a non-coronary cusp from a second valve.

However, the firm is touting two unique features of the Mosaic - the Medtronic AOA alpha amino oleic acid treatment, an anti-mineralization treatment designed to reduce calcification on the tissue valves with alpha-amino oleic acid; and the Medtronic Physiologic Fixation process, which strengthens the valve during manufacturing. According to the letter of approval for the product, AOA is a registered trademark of Biomedical Design in Atlanta.

The PMA submission was based on a prospective, nonrandomized, 1,617-patient clinical study conducted at 21 non-U.S. centers. Safety endpoints were mortality and valve-related morbidity, while effectiveness endpoints were New York Heart Association (NYHA) functional classification and hemodynamic assessments obtained by echocardiography.

Patients were evaluated preoperatively, within 30 days postoperative, 3-6 months postoperative, at one year postoperative and annually thereafter. In the study, 1,252 patients had isolated aortic valve replacement (AVR) and 365 had isolated mitral valve replacement (MVR). Results showed 85.6% of AVR patients were alive four years post-operative and 80% of MVR patients were alive four years post-operative.

Despite the mid-July approval, launch is unlikely before the fourth quarter, Medtronic said Aug. 1 in announcing the approval. The firm is attributing the delay in launching the Mosaic to the strong demand for the Hancock, and Medtronic says its sales force currently is too small to handle the promotion of both devices. The company plans to increase the size of its sales force in the next few months to compensate for the anticipated demand of the product.

However, before the firm can launch the device in the U.S., it must submit as an amendment to the PMA copies of all approved labeling in final printed form. Medtronic says it will do so the week of Aug. 14.

Approval of the Mosaic follows a firm-initiated European recall due to a misinterpretation in measurement of coaptation depth by a technician, resulting in the release of out-of-specification devices. A total of 529 units were distributed. The problem is unlikely to be repeated given it is technician-related rather than a manufacturing error, Medtronic says.

Both the Hancock II and Mosaic devices were named in a patent infringement lawsuit filed June 29 by Baxter spin-off Edwards Lifesciences against Medtronic in Wilmington, Delaware federal court. Edwards is seeking injunctive relief and damages.