BB&T Contributing Writer

ORLANDO, Florida – The 25th annual meeting of the 6,000-member North American Spine Society (NASS: Burr Ridge, Illinois) drew 3,500 attendees from more than 50 countries and featured 332 original presentations and 270 exhibitors. In his Presidential Address, Ray Baker, MD, focused on three main issues, the need for unity in the face of adversity, accountability to patients and society, and preserving trust in the physician-patient relationship. He noted that “coding and reimbursement remain a zero sum game – when one party wins another must lose. Scope of practice issues loom large on the horizon. Yet, as lines blur between and among specialties, we must remain united.“ He stressed the need to balance the social and market–based systems. “If left unchecked, market forces will dominate and the social system upon which medicine is predicated will be irreparably altered . . . if we view patients as commodities, as means to an end; they will view us the same. We are at a defining moment.“

The changing regulatory environment and spiraling downward of reimbursement are dominant issues that are impacting the introduction and marketing of spinal devices. The high cost of traversing the PMA path for new spinal implants has been an insurmountable barrier for small emerging companies, several of which closed down for lack of adequate funds, such as Applied Spine Technologies (New Haven, Connecticut), Impliant (Netanya, Israel) and Innovative Spinal Technologies (Mansfield, Massachusetts). The changing requirements for obtaining market clearance by the 510(k) route has created a cloud of uncertainty and stymied the introduction of new devices.

The spinal products market has grown increasingly competitive with a proliferation of interspinous spacers, pedicle screws, rods and plates used for dynamic stabilization, creating a challenge for companies to promote product differentiation. Two main areas of product development activity today are in minimally invasive systems (MIS) and orthobiologics for use in spinal surgery. This field was pioneered by Medtronic Spinal and Biologics (Memphis), a unit of Medtronic (Minneapolis) with its CD Horizon Sextant spinal system which allows surgeons to deliver implants to the posterior aspect of the spine without major muscle and tissue disruption that is encountered with traditional spinal fusion surgeries. A major competitor is Johnson & Johnson's DePuy (Raynham, Massachusetts) with the Viper2 pedicle screw fixation system that can be used on a wide range of pathologies, including deformity, trauma, tumor and degenerative disc disease.

Estimates of market shares in the U.S. and worldwide for spinal product companies that are reported by analysts appear below in Tables 1 and 2.

Despite the difficult environment for emerging spinal product companies, reviewed below are several innovative, mid-sized and pure play spinal products companies that are profitable and thriving.

NuVasive's (San Diego) current products include a minimally disruptive surgical platform called Maximum Access Surgery, or MAS. The company pioneered the XLIF (eXtreme lateral interbidy fusion) lateral approach which has expanded applications of lateral surgery for treating degenerative disc disease, scoliosis and spondylolisthesis. Medtronic and DePuy have since introduced lateral systems.

The use of XLIF for corpectomy (tumor vertebral body resection) was launched this year as was MAS TLIF, for a minimally disruptive pedicle-based posterior surgical approach. Today, the vast majority of posterior fusions (estimated at 80%) are open procedures, creating an opportunity for using minimally disruptive surgery. NuVasive is currently recruiting patients for a trial comparing XLIF vs. MAS TLIF for the treatment of symptomatic lumbar degenerative spondylolisthesis with or without central stenosis.

NuVasive has doubled its revenues in the past two years and focuses on developing new technologies to address specific pathologies.

Table 2. Worldwide Spine Market Share 2Q10.

K2M (Leesburg, Virginia) develops simplified solutions for the treatment of degenerative spinal conditions and complex spinal pathologies and procedures. These devices are for treating deformities and for MIS of the spine. K2M is a global company. It has entered the lateral procedure market and expanded its minimally invasive product offering with the debut of its Ravine lateral access system. This system employs a dual flat blade platform for a muscle splitting transpsoas approach and offers rigid fixation to the spine. It represents a design departure from tubular retractors. Another new product introduction is the Chesapeake anterior-lumbar stabilization system that is fabricated from PEEK polymer. It provides screw fixation through K2M's tifix locking technology, wherby each screw head forms an autogenic lock to the implant upon insertion.

K2M entered the spinal biologics market with the launch of its Vikos cervical allograft system through a strategic partnership with LifeNet Health (Virginia Beach, Virginia). The implants are designed with lordotic options for proper sagittal alignment and are treated with LifeNet Health's proprietary preservation technology for storage at ambient temperature. In 2008, K2M formed a new biomaterials division for bone grafting to substitute for metals commonly used in spinal fusions. Biological materials allow for increased cellular activity, growth and differentiation for stimulating bone formation. K2M received a strong financial boost with the announcement in July 2010 that Welsh Carson Anderson & Stowe (New York) acquired a majority position in the company. The sum was undisclosed.

Alphatec Holdings (Carlsbad, California) reported the release of PureGen osteoprogenitor cell allograft for facilitating bone regeneration. It is a highly concentrated, pure population of adult stem cells that originates in bone marrow and is collected from live, healthy donors for optimal cell functionality. It is the first pure adult stem cell to be released in the spinal market.

The company reported receipt of the CE mark for its HeliFix interspinous spacer system, a minimally invasive non-fusion solution for lumbar spine stenosis. The market size in Europe for interspinous devices was estimated at $50 million and growing at a 12% rate. The CE mark was also awarded for the Solus ALIF system, a zero-profile, single-action locking implant that is used in anterior lumbar interbody fusion (ALIF) procedures. The implant can be secured into position in a single step. The 2009 market size for anterior degenerative thoracolumnar fixation in Europe was about $45 million. Solus ALIF is under FDA review for 510(k) clearance.

The Aspida anterior lumbar plating system has 510(k) clearance and features a slim profile, a single-action self-locking mechanism and a dual-lead threaded screw which are designed to minimize the disruption of tissue and reduce operating time.

X-Spine Systems (Miamisburg, Ohio) markets devices for posterior cervical and thoracolumbar spinal procedures. The company recently launched the Fixcet spinal facet screw system that is designed to provide spinal stability for lumbar fusion procedures, including the treatment of degenerative disc disease, instability and trauma. It's one-piece screw design provides active compression of the facet joint and improved apposition of the facet surfaces compared to other systems. It can also be inserted through either a traditional open approach or a minimally invasive, wireguided approach. Also, the company will soon introduce a reduction version of its Fortex pedicle screw system and is working on an interspinous process device.

X-Spine has developed a proprietary PEEK hybrid with other materials for use in vertebral body replacement.

New products featured and launched at NASS

The NASS conference serves as a forum for launching new products or featuring innovative new products under development, and many companies took fiull advantage of an attentive audience.

Stryker (Kalamazoo, Michigan) featured its new iVAS balloon-assisted vertebral augmentation system for treating vertebral compression fractures. It is used with Vertaplex HV cement which is available in three different viscosities. It will compete against Medtronics' newly launched Kyphon Express curette that is used along with the new Kyphon cement delivery system and Kyphon's 10 bone cement with hydroxyapatite. Vertebral compression fractures are the most common osteoporotic fractures with an estimated 900,000 spinal fractures occurring annually in the U.S. The current market size for these products is estimated by analysts to be $500 million annually and projected to reach $800,000 million by 2014. The breakdown of overall sales is 60% for kyphoplasty and 40% for vertebroplasty.

Orthofix (Lewisville, Texas) had three spine product introductions this year including the Phoenix MIS modular pedicle screw spine fixation system, a line of PEEK interspinous spacers and a limited launch of its Firebird spinal deformity correction system with modularity of pedicle screw heads.

Titan Spine (Mequon, Wisconsin), a marketer of bioactive interbody fusion devices for the lumbar and cervical spine, just introduced Endoskeleton TC for cervical applications. Its acid-etched titanium surface houses osteoblast cells and participates in the fusion process by stimulating bone ingrowth (osteointegration). Similar surfaces are used on hip and knee prosthetic joints.

Intrinsic Therapeutics (Woburn, Massachusetts) markets in Europe its Barricaid anular reconstruction device that is used after limited discecetomy. It anchors into the vertebral body and supports a woven mesh barrier positioned inside the disc and against the anulus to prevent the extrusion of nucleus pulposus and reherniations. This device is the subject of an ongoing and randomized 800-patient clinical trial in five European countries which the company plans to expand into the U.S. So far there have been no re-herniations and better results for reducing low back pain and sciatica vs. a control. DFine (San Jose, California), developer of minimally invasive solutions for the treatment of vertebral pathologies, introduced in January 2010 the StabiliT vertebral augmentation system that creates a void and delivers ultra-high viscosity StabiliT ER2 bone cement to the vertebra to provide pain relief through fracture stabilization. The company has expanded its technology platform with the recently announced receipt of 510(k) clearance of its percutaneous radio frequency ablation system for localized tumor necrosis of metastatic spinal lesions. Spinal metastasis affects more than 400,000 patients and 800,000 vertebrae each year worldwide. DFine has raised $36.2 million in late-stage financing from a group of venture capital firms.

NonLinear Technologies (Or Yehuda, Israel) is developing MIS products for treating degenerative spinal conditions. Its multipurpose technology platform, Prow Suite, builds on a patented “nonlinear“ principle that allows large implants and instruments to be inserted through a small incision in the body. Its core technology consists of interconnected segments that are inserted into the body in a straight configuration, using a guide, which are then sequentially deflected. The segments form a predetermined, curved configuration in situ while the guide is used for precise positioning and as a point of inflexion for the components. Its initial device, the Prow interspinous spacer, was successfully implanted in patients with lumbar spine canal stenosis.

An expanding array of orthobiologic products

ISTO Technologies (St. Louis) markets InQu, a biosynthetic bone graft extender and substitute for use in spinal fusions. It is comprised of hyaluronic acid and polyglycolic acid. ISTO has completed enrollment in a 15-patient phase I clinical trial on NuQu, an injectable formulation of culture-expanded juvenile chondrocytes designed for the treatment of discogenic back pain and for preventing degeneration of a damaged disc. NuQu is a cell-based therapy derived from the company's platform technology for cartilage regeneration.

Advanced Biologics (Ladera Ranch, California) developed OsteoAMP (osteoinductive allogeneic morphogenic protein) to harness the various growth factors harvested from allograft tissue. OsteoAMP is available in granular, putty and sponge forms. The sponge is malleable and compressible and can accommodate a variety of interbody implants, e.g., PLIF, TLIF and ACDF.

Biocomposites (Keele, UK) introduced earlier this year its geneX ds, a fully resorbable, synthetic bone graft with a negative surface charge that stimulates bone cell activity for accelerating bone formation. It is composed of a biphasic matrix of calcium sulfate and calcium phosphate and is completely replaced by bone in 12 months. It sets in situ at body temperature in about ten minutes. The powder and liquid components are pre-packed in a dual syringe for mixing and for minimally invasive delivery. Biocomposites also markets Allogran-R, an osteoconductive beta tricalcium phosphate that facilitates trabecular bone formation and has been shown to convert in vivo to hydroxyapatite.

NovaBone Products (Jacksonville, Florida) markets a bioactive synthetic bone substitute in a variety of forms and sizes. This grafting technology delivers an osteoconductive matrix that stimulates and signals osteoblastic activity. The company showcased its newly approved MIS delivery system which provides for the delivery of bone graft substitutes through a syringe preloaded with NovaBone's putty and 6 mm diameter cannulas at varying lengths. NovaBone putty is a calcium phosphate silicate that forms an apatite surface layer that acts as a framework for osteoblast activity and new bone formation.

Osteotech (Eatontown, New Jersey) introduced this year its MagniFuse, a demineralized allograft specifically for use in the spine that contains a high concentration of bone matrix proteins MagniFuse is packed in an absorbable (polyglycolic acid) bag. The company has also launched its FacetLinx facet fusion allograft that competes against a similar facet stabilization product from NuFix (Birmingham, Alabama) for posterior spinal fusion. Osteotech is in the process of being acquired by Medtronic.

AlloSource (Centennial, Colorado), a provider of machined spinal grafts, bone and tissue, has launched AlloStem, a stem cell therapy that is an alternative to autograft. It combines adipose derived adult stem cell technology with partially demineralized cancellous bone to create an environment conducive to bone growth.

Gentis (Wayne, Pennsylvania) is developing DiscCell, a proprietary biomaterial that can be delivered minimally invasively or percutaneously, forming a viscoelastic implant. It is initially targeted for treatment of early stage degeneration of the spine. DiscCell polymerizes in-situ, is radio-opaque, and has the demonstrated ability to reconstruct the biomechanics of the affected system. It is comprised of polylauryl acrylate and barium glass. Gentis commenced human trials on DiscCell in 2007 outside the US and is currently enrolling patients in a prospective, non-randomized, single-arm, multi-center European study for the treatment of pain in post-discectomy procedures. Gentis plans to submit for a CE mark and U.S. IDE during the first half of 2011 and to initially launch DiscCell for treating symptomatic early stage degenerative disc disease and for use in lumbar post-discectomy patients.

Intralink-Spine (Georgetown, Texas) is a development stage company that uses a tissue modifying agent injected into the intervertebral disc to increase crosslinking in the native collagen matrix. It strengthens the disc tissue, provides tear resistance and increases spinal joint stability. It can be used to treat degenerative disc disease and adjacent segment disease. The technology is known as NEXT (Nonsurgical Exogenous crosslink Therapy) and is based on the human body's own natural response to heal instability and degradation of the disc.

Taking a look at PEEK and OXPEKK

Advanced Vertebral Solutions (Doylestown, Pennsylvania) reported receipt of 510(k) clearance for its steerable TLIF spinal fusion implant made from Zeniva PEEK, supplied by Solvay Advanced Polymers (Alpharetta, Georgia). The material has a modulus of elasticity close to bone, is fatigue resistance and is chemically inert.

Oxford Performance Materials (Enfield, Connecticut) featured its OXPEKK polyetherketoneketone thermoplastic polymer that is in the polyketone family which includes PEEK, a material which is widely used in implanted spinal devices. OXPEKK possesses similar stiffness to bone and is stronger than PEEK. OXPEKK has been used in implants for more than five years and such products as interspinous spacers and cervical cages. OXPEKK devices have regulatory clearances in the U.S., Europe, Korea and Brazil. The company's OsteoFab direct digital additive fabrication technology can produce custom implants directly from a CT scan and produce trabecular structures and other shapes that cannot be machined using PEEK. OXPEKK can be made radiopaque by filling it with up to 20% barium sulfate.