Medical Device Daily Associate

Corautus Genetics (Atlanta) reported that it is terminating patient enrollment in its GENASIS (Genetic Angiogenic Stimulation Investigational Study) Phase IIb clinical trial, based on the recommendation of its independent data monitoring committee (DMC).

The trial had enrolled patients with Class III or IV angina that are not suitable candidates for traditional revascularization procedures and had involved the injection of genes – specifically vascular endothelial growth factor-2 (VEGF-2) – into the heart to stimulate the formation of new blood vessels via a process known as therapeutic angiogenesis.

The DMC recommended to the company that, based on available efficacy data, enrollment should be terminated under the current protocol since, the DMC said, it saw “very little chance for significant efficacy“ as to the primary endpoint relative to the safety/risk signal it saw.

Trial termination follows enrollment suspension by the company on March 14 to investigate three recent serious adverse events that the company said it did not believe were associated with the biologic (Medical Device Daily, March 15, 2006).

The March 14 disclosure also prompted the company to cancel a planned public stock offering of 7.5 million shares at $3.85 a share. The offering had been slated for March 15.

In a conference call yesterday, the company said it will continue to collect efficacy data until the last patient previously enrolled in the trial has been followed for six months. At that time, the company plans to lock the study database and perform unblinded endpoint analyses of VEGF-2 efficacy. Safety data will be followed for a period of 12 months from the date the last patient was enrolled.

At the time of the mid-March trial suspension, 295 patients had been enrolled in the trials originally scheduled to enroll 404 patients at 30 centers in the U.S. In response to the company's action, the FDA placed the trial on clinical hold, pending review by the DMC.

The therapy had been administered into the heart using Boston Scientific 's (Natick, Massachusetts) Stiletto catheter system, a device specifically designed for the delivery of genes. The injection procedure is performed by a cardiologist in a standard cardiac catheterization laboratory.

The company currently has a distribution and development agreement with Boston Scientific for use of VEGF-2 in a delivery platform for the treatment of cardiovascular disease.

Via that arrangement, first disclosed mid-2003 (MDD, Aug. 1, 2003), Boston Sci acquired a 17% stake in the company, with the most recent stock purchase of 4.3 million Corautus shares valued at about $18 million having taken place this past June (MDD, June, 9, 2005).

Jack Callicutt, vice president of finance and administration, told Medical Device Daily that the trial setback doesn't affect its relationship with Boston Scientific at this time.

“They're still the largest shareholder of the company,“ he said, adding that they “still have the worldwide marketing rights for any of our therapeutics, and we still have a really good relationship with them.“

He noted also that both companies are committed to “fully understanding the results of this trial before we decide on the next course of action.“

As part of the process to address the FDA's clinical hold, the DMC reviewed safety information. To better consider safety in the context of risk/benefit in the trial, the DMC also requested and subsequently reviewed a limited amount of available unblinded summary efficacy data related to the increase in exercise tolerance time (ETT), which is measured by a patient's performance on a treadmill.

The primary endpoint in the GENASIS trial was improvement in ETT measured 90 days after the administration of the therapeutic.

The DMC received 90 day ETT summary data on 220 patients. It also received ETT summary data on 135 patients with six month follow-up and 26 patients with 12 month follow-up. The DMC did not review any other efficacy data.

President and CEO Richard Otto expressed disappointment in the need for trial termination, particularly in light of the promise shown in the company's earlier trials for the angina application. The study had already received two positive interim safety analysis recommendations from the DMC, with the most recent one conducted after the first 115 patients were treated in the trial (MDD, Aug. 8, 2005).

“GENASIS was really built upon Phase 1 and Phase IIa positive studies in a patient population that is defined with an unmet clinical need,“ said Otto. “And while this new information is inconsistent with our previous clinical results, the senior management team at Corautus is committed to advancing our efforts to develop the VEGF-2 therapeutic potential [and] will continue to study the therapeutic for this patient population.“

He emphasized that the trial termination does not affect the company's other ongoing Phase 1 trials being conducted primarily at Caritas St. Elizabeth's Medical Center (Boston) for the use of VEGF-2 in the treatment of peripheral artery disease and diabetic neuropathy.

Corautus CFO Bob Atwood noted that the company has about $26 million in cash and short-term investments available to it. If the GENASIS trial had continued, he said the company would have had sufficient funds to carry it through 1Q07. With the termination of that trial, he estimated that the company now has sufficient funds to conduct business through the end of 3Q07.

He added that it is “looking for ways to create additional savings to further extend that period.“

Otto said it is still too early to determine whether the trial was a failure or if it can provide insights that could yield better designed clinical endpoints and possibly lead to a new trial for angina in the future.

“We enrolled a large patient population in this trial, and we believe the data that will be generated from the trial will be sufficiently robust to allow us to draw conclusions. The ultimate story on GENASIS will not be known until all the data is received and fully analyzed.“

“It certainly is possible that there is a different endpoint that we could use to design another [angina] trial going forward,“ added Callicutt.

Corautus was created in early 2003 through the merger of GenStar Therapeutics (San Diego) and Vascular Genetics (Atlanta) in an effort to consolidate and conserve their economic and technological resources in genetic research.