Nearly one year ago, Wright Medical received the green light from the U.S. Food and Drug Administration to begin commercial sale and distribution of AUGMENT® Bone Graft, the only bioengineered alternative to autograft in ankle and hindfoot fusions.
"One of the most common operations performed in the field of foot and ankle for many years has been fusion surgery," said Christopher DiGiovanni, MD, chief of the Foot & Ankle Service Division and vice chair of the Department of Orthopaedics at Massachusetts General Hospital, Harvard Medical School.
"We have the distinct disadvantage when dealing with foot joints that we don't have replacement surgery at our disposal; and even now, we are only just starting to scratch the surface of an ankle replacement surgery that can match the survivorship of other major joints," continued DiGiovanni, the lead investigator in the U.S. for the AUGMENT Bone Graft North America pivotal trial.
With those limitations, the current standard of care for patients who have progressed past more conservative treatment options is to undergo fusion surgery. "Fusion surgery is still a very necessary part of the foot and ankle care armamentarium for many doctors and patients," noted DiGiovanni. "And the beautiful thing about these procedures is that when they successfully heal, they often last forever and represent permanent solutions."
However, he continued, "For fusion to be successful, enough of the bone on one side of the joint has to bridge to the bone on the other side to become one, but the biology behind getting these joints to heal after fusion surgery can be complicated." As a result, he said, the average rate of non-union nationwide hovers around 10 percent, with a reported range of 0-40 percent and a large subgroup of patients with additional complications skewing to the higher end of the range.
"You've got this significant subset of patients who fail fusion surgery because they just don't have the capacity to sufficiently heal the procedure; and if that happens, then you're left with an even more complicated problem," he said. "Your best shot at fusion is usually your first shot so it would be nice to maximize the chances of healing the operation by doing something which can enhance the natural healing response."
To maximize the chances of healing an arthrodesis while minimizing graft rejection, DiGiovanni said the best option previously has been autogenous bone graft. However, he pointed out, taking bone from another part of the body requires an entirely separate surgery, along with more anesthesia time and surgical risk in the operating room. "And there's really no such thing as a 'minor' surgery," he stated.
The innate surgical complication is effectively "doubled" by having to performing two surgeries instead of one, DiGiovanni explained. "Some patients heal their foot or ankle well but then wind up with issues from the autograft site ... so you've solved one problem at the expense of another problem somewhere else."
Enter AUGMENT.
How it Works
"The product consists of two primary components: Medical grade β-TCP granules and rhPDGF-BB solution," explained Eric Gay, vice president of Global Biologics Marketing for Wright Medical. "The matrix component (β-TCP) supplies the primary mode of action, providing an osteoconductive scaffold on which new cells can migrate and attach. It also serves to retain and deliver the rhPDGF-BB solution at the surgical site. "
He added, the biologic component (rhPDGF-BB) provides an active stimulus for healing through three significant modes of action: chemotaxis, mitogenesis and promotion of angiogenesis.
"The first step in the repair of damaged tissue is the migration of reparative cells to the site of injury," Gay said of chemotaxis, the process of cell attraction and migration. He continued, "Mitogenesis, also known as proliferation, refers to the process of stimulating cells to divide. Cell division increases the total number of cells and ensures sufficient numbers to provide an adequate healing response. PDGF is a potent mitogen of cells of mesenchymal (musculoskeletal) origin."
As for the promotion of angiogenesis, he added, "Regeneration of any tissue is dependent upon the availability of an adequate blood supply. PDGF is directly involved in the regulation of vascular endothelial growth factor (VEGF), a molecule which is critical for stimulating production of new blood vessels."
DiGiovanni said AUGMENT is mixed together during the surgery and then placed within "all the interstices, gaps and defects to maximize bone on bone contact across the joints being fused." He added it looks a bit like wet sand and has roughly that same type of consistency, which makes it easy to pack in and smooth down in the impacted joints. "When we're done, we have excellent apposition from one surface to the other, an objective we have proven to be very important for outcome success," he added.
Effectiveness
DiGiovanni and co-authors outlined results of the clinical trial and subsequent patient follow-up in the Journal of Bone and Joint Surgery (July 2013).
"We found that the AUGMENT was just as good at incurring healing as our old standard, autogenous bone graft, while offering the added benefit of no additional surgical risk," said DiGiovanni.
Gay said the trial demonstrated that AUGMENT was statistically significant for non-inferiority compared to autograft in 15 of 16 secondary endpoint measures at the 52-week time point. He added safety outcomes favored AUGMENT, which had fewer complications and infections compared to patients treated with autograft.
Indications & Contraindications
When AUGMENT received FDA approval on Sept. 1, 2015, it was indicated for use as alternative to autograft in arthrodesis of the tibiotalar joint and/or hindfoot - including subtalar, talonavicular and calcaneocuboid joints, alone or in combination - due to a host of conditions including osteoarthritis, rheumatoid arthritis, avascular necrosis, joint instability or deformity, congenital defect or joint arthropathy.
The product should not be used in patients who are skeletally immature, have a known hypersensitivity to any of the components of AUGMENT or who are allergic to yeast-derived products, have active cancer, have an active infection at the operative site, or have metabolic disorders known to adversely affect the skeleton (such as renal osteodystrophy or hypercalcemia) other than primary osteoporosis or diabetes.
AUGMENT should not be used in pregnant women, as the effects of rhPDGF-BB on the human fetus have not been evaluated. The bioengineered product also is not appropriate for use where soft tissue coverage is not achievable or as a substitute for structural graft.
For more complete information on indications, contraindications, safety profile and warnings, please go online to wright.com/augment.
Next Steps
For AUGMENT, Gay said following the approval for ankle and hindfoot, "It is not being used in other procedures, and there are not any current clinical trials for other uses; however Wright is currently evaluating future development opportunities for AUGMENT® Bone Graft for use in soft tissue repair and spine."
DiGiovanni noted AUGMENT and other external biologics are becoming increasingly important in medicine. In ankle and hindfoot fusion, he said the 'Holy Grail' is to achieve a 100 percent fusion rate without taking on any additional patient risks.
"The healing rates are not 10o percent in either group yet, so there's still room to grow," he said of AUGMENT vs. autograft. "But this study represents a quantum leap forward in maximizing the odds of a patient's healing a fusion site without incurring any additional surgical or anesthetic risk. We're not there, yet, but this is a great leap forward toward that day," DiGiovanni concluded.
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