Patent on the destination

When the US National Institutes of Health (NIH) put out requests for proposals for an artificial heart pump way back in 1964, the general idea was that artificial devices would be aimed at long-term use. Since the first prototypes were developed in the 1980s, the majority of these sorts of devices implanted in humans have tended to be for the short-term, as a means to allow patients with heart failure to survive until a donor organ came available.

This is still generally the case, with the majority of heart pumps or left-ventricular assist devices (LVAD), like Ventracor's VentrAssist LVAD, implanted for the short-term as a means to bridge the gap to transplant. Longer-term use, however, is about to become much more common.

Ventracor, which is in clinical trials throughout the world with VentrAssist LVAD, a third-generation centrifugal pump, has implanted over 300 of the devices in both short and long-term patients. It is conducting trials in Australia, Europe and the US, where it has a dual-trial strategy, one of which of which it has applied to patent.

As with any clinical trial, each country has its own way of doing things. The company received approval to market in Europe in December 2006 and now has many centres throughout the continent trained up to use the device. In Australia, a tiny market, the TGA granted market approval in August 2007, with five hospitals so far having implanted a device.

In the US, by far the most compelling market, they like to do things a little differently. There, the FDA requires two trials - one called a bridge-to-transplant pivotal trial, for short-term use, and one called destination therapy, for long-term use.

"The US is unique in that they decide exactly how a device has to be used," Ventracor's chief scientist and co-inventor of the VentrAssist, Dr John Woodard, says. "They have a labeling scheme that you have to stick to and they make a distinction between using our device temporarily before transplant or permanently.

"That's not the case in Europe - once you get the device approved in Europe it's up to the physician or surgeon how they are going to use it, so we have to do two separate trials in the US depending on the indications we are using it for. In Europe, you have to prove that your device does what it says it will do but in the US you have to show a benefit in a defined group of patients, and therefore the US trials tend to be much more extensive, as you have to show the statistical clinical benefit for the patient population."

Ventracor is conducting both bridge-to-transplant (BTT) and destination therapy (DT) trials, with the former much more advanced. The BTT trial is for patients on the heart transplant waiting list whose heart may deteriorate before a donor heart becomes available.

"That trial is in 140 patients, and the end-point is survival until either heart transplant or 180 days," Ventracor's CEO, Peter Crosby, says. "It is called a non-inferiority trial to an objective performance criteria - we have to achieve or exceed a performance target of 75 per cent success."

The other trial is for long-term use for people who are not eligible for transplant, due to age, co-morbidities or an episode of cancer in the previous five years. It is this trial, called EVERLAST, (or Early VERsus Late ventricular Assist devices or medical Treatment), that the company has applied to patent.

There are two arms to this trial: one involves a comparison with existing devices, such as US company Thoratec's Heartmate XVE, which the only LVAD with FDA approval for the DT indication. The other is a two-to-one randomisation of the Ventracor device versus optimal medical management, Crosby says.

"This is for people who are less sick, who are earlier in the stages of heart failure," he says. "So you have a two-thirds chance of getting this device or a one-third chance of continuing with what they have been doing. On top of that, when this trial is completed successfully our claim will be that the VentrAssist LVAD is better than the best medical management, so we think this trial offers a competitive advantage."

One reason why using LVADs for destination therapy has been so slow to take off is a bit of reluctance from the medical community. Drug therapy has improved so much that cardiologists often prefer this route, although they are coming around slowly.

"Our main competitors are not necessarily other companies like Thoratec," Crosby says. "It is drugs or apathy. The biggest competition for us is a doctor saying 'Sorry Mr Smith, you have heart failure and you're going to die in two years', instead of 'I'm sorry Mr Smith, you have heart failure but I've heard about this great new therapy, would you like to find out about it?' Our competitor is drugs or apathy, not each other."

In addition to its clinical trials, Ventracor is also undertaking a research project in association with St Vincent's Hospital in Sydney and the Alfred in Melbourne. This project is looking at ways to improve the device so that it can change its pumping speed automatically, depending on the patient's activities.

"These sorts of pumps tend to run at a constant output all the time," Woodard says. "But for those patients who exercise, they can benefit from changes in the speed of pumping, so we are currently doing a trial to see exactly how much they need to change the pump speed.

"You can change the pump speed manually but we are trying to design an optimal way to automatically and safely change the speed when the patient requires it. To change it manually you have to go into the hospital and the doctor has to do it. While a lot of patients will be fine with no adjustment, we think some of the younger and more active patients would feel better and be able to exercise more if they were able to change the speed."