Washington Editor

Aastrom Biosciences Inc. received FDA clearance to begin a pivotal trial of its regenerative stem cell product in osteonecrosis of the femoral head.

The progressive disease, also known as avascular necrosis, has no established effective treatments, and more than half the time, it leads to a total hip replacement within two years of initial diagnosis. The open-label Phase III study, which is expected to begin in the next couple of months, will enroll 120 patients at 20 sites to test the company's Bone Repair Cell (BRC) product, a mixture of stem and progenitor cells derived from a patient's own bone marrow.

"This could be the study that will grant us a label to market our product in the U.S.," said Elmar Burchardt, Aastrom's vice president of medical affairs, adding that the BRCs are one of only a few cell-based therapies to have advanced this far. "There are very few companies out there that are in Phase III studies with their cell products."

The company's trial will randomize patients to receive either the investigational treatment in combination with a bone matrix carrier following a procedure to drill a hole into the head of the femur to relieve internal pressure, or the carrier without BRC cells. On its own, that procedure to create a core track is the current standard of care for those patients.

Aastrom, of Ann Arbor, Mich., said if healthy bone can be regenerated successfully in the femoral head, the need for a hip replacement could be delayed or eliminated, eating into the number of major surgeries brought on by osteonecrosis.

"The potential is huge," Burchardt told BioWorld Today, "because you're essentially working in an indication where there is no cure, in a sense. It's a fascinating concept to be able to restore the original architecture of a tissue that's completely destroyed. It's really unique to cell therapy; you just can't do it with drugs."

The study's primary efficacy endpoint is to prevent or delay the progression of osteonecrosis to fracture, and potentially collapse of the femur head, which Burchardt said typically occurs within a year. Such effects will be measured through MRI and CT imaging. Secondary endpoints will evaluate quality-of-life measures, the use of pain drugs, mobility and measures of perfusion

Patients will be followed for two years after receiving treatment, with interim safety and efficacy analyses along the way to allow the company to make protocol adjustments. Burchardt, who said it would be difficult to forecast how long recruitment would take, noted that the transparent study design would guide expectations "as we go along."

Assuming the safety and efficacy findings are positive down the road, Aastrom plans to use the data to support a biologics license application. Going down that regulatory pathway sets a high hurdle for approval, Burchardt said, so the Phase III results might be supplemented by further findings in the indication from an ongoing, open-label study in Spain.

Initiated early this year, that trial is testing BRCs in a slightly different population of osteonecrosis patients. To date, positive but admittedly anecdotal efficacy and safety trends are being observed, Burchardt said, similar to anecdotal evidence emerging from compassionate use of the therapy in Europe.

"We have, fortunately, not seen a lot of [disease] progression," he added. "That's very encouraging data so far."

Aastrom's BRCs have orphan drug status in osteonecrosis, which involves tissues such as bone, bone marrow and blood vessels.

The BRCs are based on the company's Tissue Repair Cell (TRC) technology, which has been used in other clinical trials involving different indications to evaluate regeneration in all three of those tissues. They're culled from about 30 ml of bone marrow aspirate, which is processed over 12 days to increase the number of undifferentiated stem and progenitor cells and decrease the amount of hematopoietic cells. The latter actually are returned to a more primitive state in which they're no longer committed to making blood components, Burchardt said.

"It's the only process I'm aware of where the cells don't differentiate while they're expanding," he added.

To date, TRC-based products have been used in more than 250 patients. In addition to the osteonecrosis programs, they're in clinical trials for other bone-regeneration applications - long bone fractures and spine fusion - as well as vascular regeneration in critical limb ischemia. A prospective Phase IIb study in that latter indication just began to test a TRC-based product in peripheral arterial disease patients. The randomized, controlled, double-blind study is designed primarily as a safety trial, with secondary endpoints evaluating efficacy by measuring amputation rates, wound closure and blood flow in the affected limbs, among other things. The company also is developing regenerative medicine programs to address cardiac and neural regeneration indications.

Aastrom's stock (NASDAQ:ASTM) gained 5 cents Tuesday to close at $1.49.