A granulocyte colony-stimulating drug did not protect brain tissue or improve functional outcomes after ischemic stroke.

Researchers had high hopes for filgrastim, which is approved in Europe for chemotherapy-induced neutropenia. In vivo and in vitro studies indicated that filgrastim also had antiapoptotic properties, and stimulated arteriogenesis, neurogenesis and neurite outgrowth, said Dr. E. Bernd Ringelstein, a professor of neurology at the University Hospital of Münster (Germany).

Although the drug was safe and well tolerated, the results confirm the principal problem that has plagued the development of stroke drugs for years: They don’t make the leap from preclinical promise to clinical efficacy, he said. The results seem to echo a research saying from the 1980s: “The outlook for stroke therapy is excellent – if you’re a rat.”

The negative findings were noted in the phase II AXIS 2 trial, which randomized 328 patients with acute ischemic stroke to placebo or filgrastim (AX200) at 135 mcg/kg over 72 hours.* Study participants had to have a middle cerebral artery infarct of at least 15 cc, and be younger than 86 years old. The intent-to-treat analysis included 323 patients, 64% of whom had received tissue plasminogen activator (TPA). There was a mean of 7 hours from onset of symptoms to administration of the study drug or placebo.

The study’s primary end point was 90-day function as measured by the modified Rankin Scale. Secondary end points included 30-day lesion volume and 90-day NIHSS (National Institutes of Health Stroke Scale) score and mortality. Imaging was graded by a core lab that was blinded to the treatment.

At 90 days, the modified Rankin Scale scores were 3.26 in the treatment group and 3.06 in the placebo group. The 90-day NIHSS scores were also similar (8.8 and 8.4, respectively). Pretreatment with TPA did not significantly affect outcomes in either group. Survival at 90 days was also not significantly different, at 78% in the treatment group and 82% in the placebo group.

The initial infarct volume was an average of 46 cc. The final lesion volumes were 59 cc in the treatment group and 66 cc in the placebo group, which were not significantly different.

The most common adverse events were cardiac, endocrine, and gastrointestinal disorders, none of which were significantly more common in the treated group. AX200 did significantly increase white blood cell and monocyte counts, and slightly decreased platelets relative to the placebo, as expected, Dr. Ringelstein said.

“In summary, AX200 was a very promising drug with a comprehensive activity package. It was safe and well tolerated, but it did not provide any benefit over placebo. At the moment, we do not know the reasons for this failure, but we are exploring this with additional analyses.”

The study was sponsored by SYGNIS Biosience. Dr. Ringelstein disclosed that he was a member of the AXIS study steering board and a consultant and advisory board member for the company.

*Correction, 2/21/2012: An earlier version of this story misstated the phase of this trial.