Conversations involving news of varied implications and quality often begin with wording such as … "I have some bad news and some good news — which do you want first?"

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

Rick Wise, a Bear Stearns med-tech analyst, wrote in a report that "this strong performance bodes well for [HeartMate II] sales once launched."

Along with that news however, which the company reported Thursday, 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 was Tuesday, 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 Thursday morning conference call Gary Burbach, president/CEO of Thoratec, told listeners that "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," Burbach said.

While the company did not disclose the number of patients who were voluntarily taken off the transplant list, Wise wrote in a report that his firm estimates about 13 to 14 patients deemed by the company to be successes, having survived 180 days, but voluntarily taken off the transplant list, "while through the FDA's narrow interpretation are deemed as failures. If these patients are actually deemed failures this would put the success rate at [about] 64% and below primary endpoint threshold for success."

Wise went on to write that "while common sense and clinicians would argue that these patients should be considered even better than successes, since some have improved to the point that they are considering being weaned off the LVAD, the more conservative nature of the FDA regarding devices makes an FDA panel more likely but does not in our view make HMII approval less likely as these issues are worked through."

Wise also said in his report that these issues are unlikely to will HM II LVAD implant growth expectation following approval and launch.

"We are pushing our HMII timeline out 6 months to 1Q08 from 3Q07 to take a more conservative outlook on timing but continue to expect double digit LVAD implant growth following launch. Although we are working through the numbers, at this point we feel that a 2-3 quarter launch delay will have only minimal top line impact," Wise said.

Closing out the week with some better news, Thoratec said Friday that the FDA has approved an investigational device exemption (IDE) supplement that allows enrollment of 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.

The CAP patients will be enrolled and followed under the original protocol of the pivotal trial, the company said. It said that the addition of these patients will not impact the timing for the company's planned submission of a premarket application amendment seeking FDA approval of the HeartMate II for the BTT indication.

The HeartMate II is a continuous flow device designed to provide long-term cardiac support for advanced-stage heart failure patients. An implantable left ventricular assist system (LVAS) powered by a rotary pumping mechanism, the HeartMate II is designed to have a much longer functional life than pulsatile devices and to operate more simply and quietly, according to Thoratec. The device provides blood flow through the circulatory system on a continuous basis with only one moving part. It is also smaller and easier to implant than pulsatile devices.

Data released from the BTT arm of the HeartMate II trial last month at 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.

There were no reported mechanical pump failures. The data showed that the trial met or exceeded the objectives for the secondary endpoints, including frequency of adverse events, improved functional status and enhanced quality of life. The mean support duration for patients in the BTT trial was 169 days, with one patient supported by the device for 600 days, or 20 months. The patients ranged in age from 18 to 69 (Medical Device Daily, April 2, 2007).