Aastrom Biosciences, Inc. the leading developer of patient-specific, expanded multicellular therapies for the treatment of severe, chronic cardiovascular diseases, announced that it has reached agreement with the US Food and Drug Administration (FDA) on the Special Protocol Assessment (SPA) for the design of the phase III REVIVE-CLI clinical trial of ixmyelocel-T, the company's expanded multicellular therapy, in patients with Critical Limb Ischemia (CLI) who have no other treatment options.

Aastrom's phase III clinical trial will enrol up to 594 no-option patients with CLI at approximately 80 clinical sites across the US. This multi-centre study will be randomized, double-blinded, and placebo-controlled and will include only CLI patients with existing tissue loss (e.g., ulcerations and/or dry gangrene). In the US, there are approximately 250,000 CLI patients with tissue loss. Patients with CLI who have tissue loss are five times more likely to experience an amputation within 12 months of diagnosis.

“We greatly appreciate the guidance and support of the FDA staff, our phase II investigators and our phase III steering committee who have helped us reach final agreement on the SPA, a critical component to advancing ixmyelocel-T into phase III clinical testing,” said Tim Mayleben, president and CEO of Aastrom. “The SPA from the FDA confirms our confidence that the design of the phase III clinical trial is suitable to support BLA approval for ixmyelocel-T in this under-served patient population. Given the positive results from our RESTORE-CLI phase II b trial, we have a great deal of confidence in our phase III programme and look forward to launching this pivotal study in the fourth quarter of this year.”

CLI is the most severe form of peripheral artery disease, leading to over 160,000 limb amputations per year in the US. Approximately 25% of patients will die within the 12 months following diagnosis, and fewer than 25% of patients survive more than four years. Today, there are approximately 400,000 no-option CLI patients who have limited therapeutic and surgical options. Outcomes for these patients are extremely poor, especially those with existing tissue loss (patients classified as Rutherford 5).

In the RESTORE-CLI phase II b clinical trial, which was the largest fully controlled cell-therapy study ever conducted in CLI, patients who received treatment with ixmyelocel-T showed a favourable safety profile and clinically meaningful and statistically significant benefit in time to treatment failure events. Aastrom expects to present the data from the RESTORE-CLI phase II b clinical trial at a major medical meeting in November 2011.

A SPA is a formal, written agreement between the FDA and a drug sponsor concerning clinical trial design, endpoints and other clinical trial issues that are used to support regulatory review and approval of a therapeutic product candidate. The process is intended to increase the likelihood that if the specified clinical trial protocols from the SPA are followed, the clinical trial endpoints are achieved and there is a favourable risk-benefit profile, trial data may serve as the primary basis of an efficacy claim in support of a Biologic License Application (BLA).