Biologics – Where’s the Damn Evidence?
Source: Wikimedia Commons and Billy Baque SeaSpine’s Drop the Mic Moment at NASS
Other companies are also putting evidence at the center of their biologics marketing.
One that deserves special notice is SeaSpine, Inc.
SeaSpine, using their scientific advisory board, designed a simple test for bone formation which can be used for either BMP or non-BMP biologics.
“We wanted to isolate the elements which can form bone, regardless of the biologic implant”, said Frank Vizesi, Ph.D. Vice President, Orthobiologics Research & Development, and Clinical Affairs at SeaSpine.
“We designed a study to test whether demineralized bone matrix (DBM) with or without BMP proteins can form bone. With growth factors, we got abundant bone formation in an athymic rat muscle pouch model. Without growth factors we got NO bone formation.”
Simple. As far as it goes. SeaSpine and their surgeon advisors then took it a step further, teaming up with Jeff Wang and his research team at USC.
“Nobody had presented data which isolates the elements of living cell-based implants to prove the cell component actually forms bone,” said Dr. Vizesi.
The study: “What drives spinal fusion within graft materials: cells or growth factors?”, by Aidin Abedi MD[1], Blake Formanek BA1, Nick Russell PhD[2], Frank Vizesi PhD2, Scott Boden MD[3], Jeffrey C. Wang MD1 and Zorica Buser PhD1, was presented to spine surgeons and a group of Wall Street analysts and institutional investors at the 2019 annual meeting of the North American Spine Society.
“So, the first question a surgeon might have is ‘are the cells alive?’. There is plenty of data that says they are. But is that the right question?”
The right question, said Vizesi, was “do the cells DO anything?”
Using the well-validated athymic rat model, the study team took 2 of the 3 top selling living cell-based bone grafting products and tested them with cells and then without cells.
It was, of course, a variation on the well-known athymic rat model test of DBM.
As Dr. Vizesi explained to OTW: “We tested with and without the cells. So, with the cells these products should work better for bone formation. It’s not complicated.”
What the investigators found, and what they presented at NASS, was that neither of the living cell-based products (which out-sell classic DBM) produced an increase in the rate of bone formation and, therefore, fusion.
As Dr. Vizesi told OTW, “Whether with cells or without cells, the amount of bone formation was the same.” Meaning that the cells didn’t add anything to the fusion. If that’s the case, then they might actually be diluting the performance of the products.
“Our basic conclusion is that it is the DBM that is causing an increase in bone formation and fusion.”
Not living cells.
As we’ve said many times, biologics is complicated. There is more work to do.
Still, this study is a drop-the-mic moment.
The Regulators are Closing In
Under the FDA’s Human Cell and Tissue (361) rules, human tissues may be processed for clinical use and commercialized IF their use is homologous and safe—no disease transmission, principally.
In practical terms that means rigorous, validated processing and no therapeutic benefit marketing claims.
Only biologic products with a biologics license (BLA) or pre-market approval (PMA) may claim a therapeutic benefit.
A recent study found that a depressingly large amount of non-BMP marketing emanating from clinics and suppliers alike had crossed that FDA imposed marketing claims and practices line.
Every clinic that is promoting non-BMP biologics should carefully review its claims, both implicit and explicit.
The good news is that AAOS and other surgeon societies are providing guidance so that clinics and suppliers can stay on the right side of both medicine and, critically, the law.
Still, forewarned is forearmed.
[1] Keck School of Medicine, University of Southern California
[2] SeaSpine, Inc
[3] Emory University School of Medicine
