As we near the end of the second decade of the 21st century, it has become increasingly clear that we have entered “The Age of Biology.” With the 19th century coined as “The Age of Engineering” and the 20th century referred to as “The Age of Chemistry and Physics,” we see that the pace of technology evolution today is accelerating even faster as a result of those foundations. In the field of orthopaedic surgery, over the last 100 years we have migrated from therapies based on limb removal to joint replacement to tissue repair, and we are beginning to see clinical solutions for tissue regeneration. These four Rs represent the history and future of clinical orthopaedics.
Products whose function is to drive repair or regeneration of musculoskeletal tissue are classified as orthobiologics, and are typically based upon some combination of biomaterials, signaling molecules and cells. Each of these components may be derived from the patient, a cadaveric or animal tissue source, synthetic materials or advanced biotechnology manufacturing processes. The explosion of publicity around these scientific advances has given rise to a more informed patient population that, in conjunction with their desire to remain active into their later years, seeks solutions to “regenerate” their damaged or aging tissue. As such, this market space is expanding in terms of the number of:
- patients seeking early intervention,
- variety of procedures being performed, and
- new companies and product introductions to address this demand.
The dynamic is exciting and full of promise on one hand, but also filled with uncertainty and critical challenges on the other.
During 2017, a dramatic increase occurred in the number of firms offering cell-based therapies for bone and cartilage repair, with still others promoting the same for soft tissue. The array of options, ranging from bone marrow-, fat-, placenta-, amniotic fluid- and allograft-derived cells is dizzying, and further complicated by the evolving FDA and EMEA regulatory landscape. Fortunately, a clear set of FDA guidance documents were published in 2017, which puts many of these unproven products out of compliance and subject to enforcement sanctions. The clinical and scientific data supporting many of these products lags behind the expectations of surgeons, hospitals and third-party payors, thus creating a conflict between what patients perceive as the cutting-edge cure and what clinicians are able to offer. Adding to this dilemma is the fact that many of these human cellular and tissue products may be legally marketed without substantial investment from developers, who are then reticent or unable to invest deeply in the creation of high-quality clinical data. For this reason, the clear winners in this space over the long haul will be those firms that have the foresight and commitment to invest in the generation of rigorous evidence to satisfy surgeons, hospitals and insurance companies.
New biomaterials for articular cartilage and soft tissue repair are making their way to the U.S. clinic through the traditional, long-term premarket approval pathway, and short-term 510(k) pathway, respectively. Fortunately, several of these initiatives are already commercially available outside of the U.S., which serves to jump-start the collection of clinical data and may accelerate their approval by FDA. As we advance our sophistication regarding the performance of these materials, it must be met with equally innovative modes of implant delivery to protect the surrounding tissue necessary to support an optimal healing environment. The combination of such minimally invasive surgical approaches with well-understood biomaterials and clinical outcomes is on the near-term horizon of providing solutions with elegant simplicity.
This year marks the 15th anniversary of the launch of BMP-2, which is undeniably the most commercially successful orthobiologic product ever sold. And while this product still enjoys a multi-hundred million dollar revenue stream, industry veterans have not forgotten the story of its lengthy and gargantuan investment requirement, meteoric rise and subsequent halving of revenue as a result of adverse events, litigation and claw back on off-label use. Still, competing with such an effective product for on-label indications is extremely challenging, and therefore, the small number of firms that have the appetite to invest in peptides or recombinant proteins are attempting to gain FDA approval in smaller indications with claims of improved safety or cost savings. One such peptide product was approved in 2017, but few others are on the near-term horizon.
In conclusion, the orthobiologic field has made substantial progress over the last 25 years, and now enjoys a respectable revenue stream of $5 billion worldwide. This comprises a small number of multi-hundred-million dollar products (e.g., BMP, allogeneic cellular bone grafts and viscosupplements), and a vast array of smaller products that often lack a clear sponsor-defined algorithm for when and where to use (e.g., PRP vs. cells vs. allograft vs. synthetic granules, blocks or putty for bone repair). Technology is advancing, but requirements for market entry and adoption remain high, and those who wish to succeed would be well-served to: abide by FDA guidance, invest in development of high quality indication-specific evidence, and possess the patience to do both.
In most cases, the large companies are not investing their R&D resources into such products, but are more inclined to pay a premium to acquire smaller companies that successfully navigate the development, clinical and regulatory labyrinth to market. Clearly, “The Age of Biology” is upon us, and here to stay, but the traditional orthopaedic market will absolutely remain the core of our industry for the foreseeable future.
Scott P. Bruder, M.D, Ph.D., founded the Bruder Consulting & Venture Group in 2015 after 25 years in the industrial sector, serving in the C-Suites of Stryker as the Chief Medical and Scientific Officer, and at Becton Dickinson as the Chief Science and Technology Officer. Previously, while at Johnson & Johnson, he and his team built a portfolio of tissue repair products for the DePuy franchise before establishing J&J Regenerative Therapeutics. Earlier in his career, Dr. Bruder was the first scientist hired by Osiris Therapeutics; he patented their approach to focus on allogeneic mesenchymal stem cells as a therapeutic platform. Dr. Bruder has also served as Professor of Biomedical Engineering at Case Western Reserve University since 2011, after 13 years as adjunct faculty in the Department of Orthopaedic Surgery. He can be reached via email or bruderconsulting.com.