By Brady Huggett
Chiron Corp. didn't reach statistical significance for its primary endpoint in its Phase II trial with recombinant fibroblast growth factor-2 protein in peripheral artery disease, but it saw positive data trends in this relatively new field.
The fibroblast growth factor-2 protein (FGF-2) multicenter, placebo-controlled, double-blind study was designed to test safety, efficacy and dosing regimens of FGF-2 patients with moderate to severe claudication - leg muscle pain while walking - due to peripheral artery disease, or PAD. The primary endpoint was peak walking time, or PWT, measured by walking on a treadmill.
"Clearly we didn't hit with gold stars, but we showed benefit in clinical measures," said Shelley Schneiderman, associate manager of corporate communications and investor relations at Chiron. "Growing new blood vessels, it's an emerging field, and these are the first studies to show improvement. The question is, 'What can we do next in this field to prove this can be a valuable therapy?' Our next test will be to maximize the signals we have seen in an additional trial."
Chiron, of Emeryville, Calif., presented results at the American Heart Association Scientific Conference on Therapeutic Angiogenesis and Myocardial Laser Revascularization in Santa Fe, N.M. Compared to baseline PWT, the single-dose patient group demonstrated a 34 percent increase in PWT at day 90, vs. a 20 percent increase in those patients receiving a double dose of FGF-2 and a 14 percent increase in patients in the placebo arm. However, in a pair-wise comparison, patients treated with a single dose of FGF-2 demonstrated a significant increase in PWT at day 90 vs. placebo (p=0.026).
The prespecified primary efficacy analysis (comparing both single and double doses of FGF to placebo) of change in PWT at day 90 showed a positive trend but did not achieve statistical significance (p=0.075).
"Getting .075 in a Phase II trial is regarded as encouraging results," Schneiderman said. "In the analysis, instead of linking the FGF groups, we looked at them separately, which is where we saw the statistically significant .026, in the single-dose study."
Other secondary endpoints, such as claudication onset, ankle brachial index and two validated quality of life measures, did not achieve statistical significance, but positive trends were evident in several measures.
Chiron also presented the 180-day results of its Phase II trial of FGF-2 in patients with coronary artery disease (CAD). Statistical significance was not achieved at 90 or 180 days for exercise tolerance, but the trial showed improvement over placebo at day 90 in several endpoints, including reduction in angina frequency.
"[Reduction in angina frequency] is what we call a clinically relevant secondary endpoint," Schneiderman told BioWorld Today. "It was statistically significant at 90 days, but directionally positive at 180.
"It was interesting how the trials were put together," she added. "In the CAD, that was a dose-finding study, we tested three doses, all administered as one dose. In the PAD, that was regimen finding, one dose of FGF either was given once or given twice. So, we were able to compare apples to apples a bit. And we plan to use both [studies] to make our assessment for the next step."
Schneiderman said Chiron has several avenues when considering where to go next.
"We have a few options, and they are all open to us," she said. "We could go to Phase III, we could do another Phase II, but we aren't ready to make a decision on that yet. Clearly, we want the decision to be timely, but we want it to be the best decision."
Separately, Chiron released news that the European Patent Office Board of Technical Appeals upheld the validity of Chiron's European HIV patent aimed at polypeptides and polynucleotides from the envelope and core domains of HIV-1. The polypeptides and polynucleotides are used in both immunoassays and nucleic acid probe-based clinical diagnostic and blood-screening products. The decision allows a $20 million sum to be paid to Chiron from F. Hoffmann-La Roche Ltd., of Basel, Switzerland, covering a nonrefundable license fee and royalties for prior infringing sales.
"The decision cements what we already agreed to," Schneiderman said. "This happened and the outcome was favorable to Chiron and we will realize some monies for it."
Chiron's stock (NASDAQ:CHIR) moved up $1.187 Monday to close at $46.187.