Editor’s Note: This is an article that first appeared in the December issue of Market Spotlight in BoneZone. With some changes from the original article, Orthopedics This Week is proud to publish Dr. Bruder’s excellent review and commentary and to lend its name along with BoneZone and other responsible journals in the orthopedic community for increased scrutiny of orthobiologic therapies which are woefully lacking in clinical evidence.
The field of orthobiologics has made substantial progress over the last 25 years, and now enjoys a meaningful revenue stream of $5 billion worldwide, according to ORTHOWORLD estimates.
Through the first half of 2019, orthobiologics revenue reported by public companies has grown just under 2%, slightly lagging the growth rate of orthopedics overall. Were it not for declining viscosupplement sales, resulting from a combination of the AAOS’ [American Academy of Orthopaedic Surgeons] controversial recommendation against their use, and the cash sale of alternative products from private companies, orthobiologic revenue growth from public companies would have eclipsed the overall market by several percentage points.
Notwithstanding this ~5% year-over-year decline in viscosupplementation, a handful of products within this category (including injectable hyaluronic acid) still generate outsized revenue contributions (Infuse/BMP-2, SYNVISC, ORTHOVISC). The rest of the segment is characterized by a vast array of lower revenue products which often lack a clear sponsor-defined algorithm regarding when and where to use (e.g., autologous platelet rich plasma or bone marrow concentrate for musculoskeletal indications, allogeneic cellular grafts for bone repair, demineralized bone, synthetic bone graft substitutes).
Our collective scientific understanding and clinical experience with these products continues to evolve; however, the requirements to properly introduce new technologies for market entry and adoption remain high. Companies seeking commercial success would be well-served to abide by FDA guidance and invest in developing high quality indication-specific evidence and possess the patience to do both. Of course, subtle variations on this theme exist depending on the product Class (II or III), whether the cleared or approved marketing claims are general or indication-specific, and whether such products are allograft human tissues, which are necessarily sold without providing any specific claims of performance. In the last case, a desire to make specific claims would change the regulatory pathway from a banked human tissue to a medical device, or possibly a biologic, depending on the exact structure and function of the allograft.
The “New” Product Development Paradigm
In order to drive the discovery, development and commercialization of effective therapeutic products into routine clinical practice with greater speed, certainty and financial efficiency, a functional relationship between academic and industrial investigators is essential. Approaches that successfully weave the technology, tools and clinical applications from the laboratory bench to the clinical bedside stand a greater chance of being successful in the marketplace. In the case of new biologic solutions, and human cellular and tissue products (HCT/Ps) in particular, demand grows for not only basic scientific evidence but a demonstration of clinical efficacy to support utilization and reimbursement. While different hurdles exist depending upon the nature of the product (e.g., device vs. HCT/P) and the regulatory burden necessary for market launch (e.g., 510(k), PMA [premarket approval] or BLA [biologics license application]), it is becoming incumbent on the research community (including both company sponsors and independent investigators) to provide ever more compelling evidence of clinical and economic benefit.
Myriad reasons underlie this growing demand for evidence, which stems from 1) the importance of ensuring patient safety above all else, especially in the face of, 2) increasing sophistication of, and competition for patients amongst, orthopedic surgeons and non-operative physicians, 3) economic constraints imposed by Medicare and third party payors who appropriately depend on evidence-based-medicine, and 4) a growing backlash from our professional societies (e.g., AAOS, NASS [North American Spine Society], ICRS [International Cartilage Regeneration & Joint Preservation Society]) noting that high quality studies are necessary to render endorsement.
Unfortunately, in the race to capitalize on patient-driven interest in so-called “stem cells,” biologic therapies and “regeneration” of a more vital, healthy and functional body, an explosion of new suppliers have brought new products to market which lack scientific controls, validity and meaningful evidence. The opportunistic avarice of companies and physicians in response to patient demand has led to mercenary behavior that has begun to sully the field’s reputation. New regulatory guardrails, and a return to conscientious management of our precious healthcare resources could, we think, swing the pendulum back to a state of more principled product promotion and patient care.
