Wyeth gets FDA approval for a novel protein device that enhances bone healing

May 3 2004

Wyeth have announced that the FDA has approved rhBMP-2/ACS (recombinant human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge), a novel protein device that enhances bone healing, for use in the treatment of acute, open tibia shaft fractures in adults. The device consists of rhBMP-2 placed on an absorbable collagen sponge. It will be used after stabilization with an intramedullary nail (a metal rod inserted into the bone) by orthopedic surgeons, after appropriate wound management.

"This unique protein represents a breakthrough in orthopedic surgery as it can help improve fracture healing, while reducing the chances of infection," says Joseph Camardo, M.D., Senior Vice President of Global Medical Affairs and
Medical Director for Wyeth Pharmaceuticals North America. "It clearly represents a novel approach to orthopedic surgeons facing a serious tibia fracture."

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2, or dibotermin alfa), a recombinant version of a naturally occurring human protein, was discovered and developed by Genetics Institute, now part of Wyeth. The protein is manufactured at a Wyeth biopharmaceutical facility in Andover, Massachusetts.

The data package Wyeth submitted to the FDA was based on one of the largest orthopedic fracture clinical trials ever conducted. The use of rhBMP-2/ACS 1.5 mg/mL in more than 400 patients during surgery, significantly improved the probability of fracture healing as evidenced by a reduced need for secondary procedures to promote fracture healing, when compared to the standard of care, fracture repair using an intramedullary nail.

In 2002, the European Commission approved the Marketing Authorization Application (MAA) for rhBMP-2/ACS for use in the treatment of acute tibia fractures in adults in the European Union (EU). Marketed under the name InductOs(TM), this product was introduced in the EU in July 2003.

Medtronic Sofamor Danek (MSD) will be marketing the product for tibia fractures, while purchasing the rhBMP-2 from Wyeth. Wyeth will receive royalties and milestone payments from MSD.

Wyeth and MSD reached an agreement to expand Medtronic's marketing rights for rhBMP-2/ACS in the United States, Canada, Australia, Latin America and other countries, for spine and tibia fracture indications.  Medtronic will also have global marketing rights for the tibia fracture indication.

rhBMP-2/ACS must be applied within 14 days after the initial fracture. Like all implanted medical devices, rhBMP-2/ACS may have side effects. The most frequent side effects included: 

• abnormal healing at the surgical site;
• abnormal lab tests which included those related to pancreas and liver function, anemia, and decreased concentrations of calcium and potassium;
• constipation;
• nausea and vomiting;
• allergic reactions at the surgical site;
• infections at the surgical site;
• local and surgical site inflammation;
• altered mental status;
• altered sensations at the surgical site;
• and respiratory difficulties.

Some patients in the clinical trial who were treated with rhBMP-2/ACS 1.5 mg/mL had an antibody response to either rhBMP-2 (9 patients) or the ACS (29 patients).  Because of the small numbers of patients who developed antibodies,
it was not possible to determine if there was a connection between the antibody formation and the need for additional treatment to heal their fracture.

Among the less frequent side effects, some patients (6 percent) treated with rhBMP-2/ACS had abnormal bone healing at the fracture site.

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