ImaRx Therapeutics Inc. brought its Phase I/II stroke trial to an early close after interim data showed an increase in intracranial hemorrhage events in patients receiving two vials of MRX-801 microbubbles combined with ultrasound and tissue-plasminogen activator (tPA).

Shares of ImaRx (NASDAQ:IMRX) fell 35 cents, or 19 percent, to close at $1.50 on Friday.

Yet the news wasn't all bad. In fact, ImaRx President and CEO Bradford Zakes characterized the early termination of the trial as positive.

In the first cohort of the randomized, placebo-controlled trial, six patients received tPA alone and 12 patients received a single vial of MRX-801 along with ultrasound and tPA. No unexpected safety events occurred, and patients receiving MRX-801 demonstrated signs of increased blood flow in the occluded artery, known as recanalization. Although clinical and neurological evaluations were similar for both groups at 24 to 36 hours, the MRX-801 group showed clinical improvements according to Modified Rankin analyses conducted 90 days post-treatment.

The encouraging initial data prompted ImaRx to move on to the second cohort, in which six patients received tPA alone and 11 patients received two vials of MRX-801 along with ultrasound and tPA. Initial safety data in the second cohort found an increase in intracranial hemorrhage events in the MRX-801 group, prompting the company to end the study and scrap plans for the third and fourth cohorts, which would have looked at even higher doses.

Garen Manvelian, chief medical officer of Tucson, Ariz.-based ImaRx, said tPA is "known to cause bleeding," and the affect "could have been multiplied" by adding MRX-801.

TPA, marketed by Genentech Inc. as Activase, is the only FDA-approved treatment for stroke. The drug triggers an enzyme cascade that dissolves blood clots, but it increases hemorrhage risks and must be administered within three hours of a stroke, making it applicable only in about 3 percent of patients.

Enzyme-based alternatives to tPA have faced setbacks but still are moving forward.

Paion AG's clot-buster desmoteplase failed a Phase III stroke trial and got dumped by partner Forest Laboratories Inc. last year, but H. Lundbeck A/S recently picked up the compound and may start another Phase III later this year. Meanwhile, Nuvelo Inc. started a Phase II stroke trial last month with the thrombolytic drug alfimeprase, which previously had failed two Phase III studies in peripheral occlusion and catheter occlusion, resulting in the loss of partner Bayer Healthcare AG. And Neurobiological Technologies Inc. is plugging along with two Phase III stroke trials with its clot-buster Viprinex (ancrod). (See BioWorld Today, Jan. 19, 2007, June 28, 2007, and Jan. 2, 2008.)

All three drugs are designed to extend the window after stroke within which treatment can be administered. Desmoteplase and alfimeprase are both intended for use within nine hours, while Viprinex would be used within six hours.

ImaRx takes a "simple yet elegant" approach to clot busting that is "very different" from others in development, Zakes told BioWorld Today. The MRX-801 microbubbles are designed to penetrate the blood clot, releasing mechanical energy that works with ultrasound to break up the clot. Although administration timelines have yet to be finalized, Zakes said it is "certainly reasonable" to envision testing the approach up to six or possibly nine hours after stroke.

ImaRx initially tried its mechanical approach, dubbed SonoLysis, in combination with tPA's enzymatic approach because the two were believed to be complimentary, Zakes said. But future trials will use only MRX-801 and ultrasound. ImaRx currently is working with Royal Philips Electronics to optimize the ultrasound parameters for such a trial, which is scheduled to begin in the second half of the year.

Final data from the first and second cohorts of the Phase I/II tPA trial also are expected in the second half of the year.

Although other companies have approached ImaRx about applying the SonoLysis technology in other applications, Zakes said his team remains focused on stroke for the time being.

The only other product in ImaRx's pipeline is urokinase, an FDA-approved thrombolytic licensed from Abbott for use in pulmonary embolism. Sales of the drug brought ImaRx about $5.7 million in revenues during the first nine months of 2007. The company ended the period with $16 million in cash, equivalents and marketable securities.