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Current & Critical

Orthobiologics Activity Signals Collaborations and Clinical Data Essential for Company Growth

By Julie A. Vetalice

ORTHOWORLD estimates that global orthobiologic product sales account for ~10% of the orthopaedic market’s revenue, overall. In 2016, that translated to just over $4.9 billion, an increase of 3% vs. 2015. For this year and into 2019, we’re projecting similar growth. 

Supporting this growth will be patients who continue to seek non-surgical alternatives for joint repair, and continued growth in the use of synthetics and stem cell-based products. Collaborations will remain attractive in the space as companies choose orthobiologic-focused partners to get products to market, and universities partner with companies on licensing and development. Robust clinical and economic data will be a requirement for product clearance and adoption. These strategies were among our stated market observations in THE ORTHOPAEDIC INDUSTRY ANNUAL REPORT®, and activity thus far in 2017 reaffirms our stance. 

We’ve compiled year-to-date activity through the second week of October 2017—M&A, collaborations, funding, data—to show how your competitors and customers have responded to market demands. 

Exhibits 1 and 2 illustrate who acquired or partnered with whom so far, this year. 
 

Exhibit 1: Merger & Acquisition Activity

 Acquirer  Acquired Description
 Kuros Biosurgery  Xpand 
 Biotechnology
 
 Kuros gained access to MagnetOs synthetic bone graft putty, which in 3Q17
 received FDA 510(k) clearance as an autograft extender in the
 posterolateral spine.
 
 Stability Biologics’ 
 stockholders
 MiMedx’s
 Stability
 Biologics assets
 
 After acquiring Stability in 1Q16, MiMedx leadership determined in 3Q17
 that the portfolio was not a strategic fit with its new focus on becoming a
 biopharmaceutical company and returned the company to previous
 stockholders. MiMedx will retain access to Stability sales reps via private
 label distribution agreement.
 
 Organogenesis   NuTech Medical  
 NuTech’s portfolio includes Affinity fresh amniotic allograft; NuShield
 dehydrated terminally-sterilized allograft and NuCel and ReNu
 cryopreserved allografts. NuTech will continue existing operations as a
 division of Organogenesis, focused on surgical biologics.
 
 Tissue Regenix
 (TRX) 
 CellRight
 Technologies

 
 Combined, the companies will offer products for bone and soft tissue
 regeneration based on CellRight’s human-derived bone grafts and TRX’s
 dCELL decellularization platform. Purchase price $30.0MM. 

 

Exhibit 2: Collaboration Activity

 Parties  Description of Collaboration
 AlloSource, Stryker  
 Stryker will distribute AlloSource biologic products in the U.S. for use in sports medicine 
 procedures. 
 
 Amend Surgical,
 Univ. of Florida
 
 Amend Surgical will exclusively license patents for the development of Biomimetic Bone.  
 
 ARTOSS,
 Owens & Minor
 
 Artoss entered into a Defense Acquisition Purchasing Agreement with Owens & Minor and
 gained U.S. Department of Defense access to NanoBone bone graft. 
 
 Bioventus,
 MEDSERVICE
 
 Bioventus selected MEDSERVICE to distribute DUROLANE single-injection joint fluid in
 Russia. 
 
 Bioventus, Premier  
 Premier is now offering Bioventus’ full surgical orthobiologics product portfolio to its U.S.
 membership, comprising 3,750 hospitals and >130,000 provider organizations. 
 
 Bone Biologics, UCLA  
 Bone Biologics entered into an exclusive license agreement with UCLA for global
 application of NELL-1 protein, with an initial focus as a bone graft substitute for
 spine fusion.
 
 Bone Therapeutics,
 Asahi Biomet
 
 Asahi Kasei will exclusively develop and commercialize PREOB autologous bone cell
 therapy in Japan for the treatment of osteonecrosis of the hip and potential future
 orthopaedic applications. 
 
 BONESUPPORT,
 Zimmer Biomet
 
 An extended U.S. distribution agreement allows Zimmer Biomet to continue its exclusive
 rights for CERAMENT BONE VOID FILLER products for orthopaedics, trauma and
 foot/ankle indications. 
 
 DePuy Synthes,
 Orthocell
 
 Under terms of a research collaboration agreement, a joint multi-center Australia study
 of Ortho-ATI stem cell treatment for tendon and ligament regeneration commenced
 in 1Q17. 
 
 LifeLink Tissue Bank,
 HCT Regenerative
 
 LifeLink Tissue Bank will provide allografts to treat sports, orthopaedic and spine injuries
 to HCT Regenerative, for distribution in Taiwan. HCT, established in 2016, is the first
 company in Taiwan to process human tissue into regenerative biomaterials for
 clinical use. 
 
 Seikagaku, Ono
 Pharmaceutical
 
 Co-development and marketing collaboration in Japan for SI-613 for the treatment of
 osteoarthritis. 
 
 Vericel, Orsini
 Pharmaceutical
 
 Two-year renewable agreement for distribution of Carticel and MACI in the U.S. and
 Puerto Rico. 
 
 Vericel, Innovative
 Cellular Therepeutics

 Innovative Cellular Therapeutics gained exclusive rights to develop and distribute Carticel
 and MACI in Southeast Asia. 
 

 

Of the 34 transactions that we’ve reported to date this year, orthobiologics were involved in eight. Exhibit 3 shows where dollars were spent.
 

Exhibit 3: Funding Activity

 Amend Surgical  
 Funding agreement with The Florida Institute for the Commercialization of Public
 Research addressing newly-licensed technology developed at the University of
 Florida, in support of products for the bone graft substitute market.
 
 ASC Biosciences  
 Partnered with Stem Cell Development Fund to receive $1.5MM to support
 development and marketing of its Multipotent Adult Stem Cell platform. 
 
 BONESUPPORT
 Commenced trading as BONEX on Nasdaq Stockholm following completion of its
 IPO.
 
 Carmell Therapeutics
 Closed a $4MM Series B financing in support of Phase III clinical development of
 its Bone Healing Accelerant.
 
 Cerapedics
 Closed a $20MM senior secured term loan that will support commercialization of
 i-FACTOR bone graft for ACDF and fund an FDA study on its application in TLIF.  
 
 DiscGenics
 Closed a $14MM Series B financing to support regulatory approvals and
 manufacturing ramp-up for Phase III clinical and commercial production
 of its cell therapy for treatment of degenerative disc disease. 
 
 Hyalex Orthopaedics
 Raised $16MM in a Series A financing. Hyalex is developing HYALEX synthetic
 polymer that is designed to mimic hyaline cartilage, to potentially replace only
 diseased areas of joints while sparing healthy bone. 
 
 Providence Medical Technology
 Closed a $10.5MM debt agreement that will support distribution of cervical fusion
 technology in U.S. and ex-U.S. markets. 
 

 

Clinical data on the cost/benefit of orthobiologic treatments is required to gain product clearance and adoption. This last section details clinical trials and studies.

Hip/Knee

Andrews Institute for Orthopaedics & Sports Medicine and the Andrews Research & Education Foundation are facilitating a randomized, multi-center Phase II U.S. FDA-observed clinical trial evaluating use of a patient's own stem cells to regenerate knee cartilage. This is reportedly the first time that stem cells will be evaluated in a clinical trial for the ability to regenerate cartilage in massive knee cartilage injuries. The 6-year study may end early if results indicate statistical significance.

Studies indicate that Anika Therapeutics’ HYALOFAST scaffold + autologous adult MSCs present a viable option to treat knee cartilage lesions, regardless of patient age. 

Phase III study results demonstrated that Anika’s CINGAL provided superior immediate and short term OA pain relief after injection vs. hyaluronic acid alone, and superior relief at 26 weeks vs. saline. 

Bone Therapeutics completed patient recruitment for interim analysis in its Phase III trial of PREOB for the treatment of hip osteonecrosis. 

Results from Phase I and Phase II study indicate that Histogenics NeoCart tissue-engineered implant is a safe, effective treatment for articular cartilage lesions through 5-year follow-up. 
 

Spine

Results from ovine study of Bio2 Technologies’ Vitrium bioactive glass demonstrated the device’s capability to support interbody fusion. 

Interim results in a Phase IIA trial with Bone Therapeutics’ ALLOB showed evidence of successful spinal fusion and statistically significant improvements at 12 months. 

Burst Biologics received IRB approval for a U.S. prospective clinical study of BioBurst cellular allograft in spinal fusion. 

Follow-up data from an IDE clinical trial of Cerapedics’ i-FACTOR bone graft indicated statistical superiority to autograft in ACDF. 

FDA accepted DiscGenics’ Investigational New Drug Application for a clinical study of its cell therapy product candidate to treat degenerative disc disease. 

Medtronic launched a long-term global clinical study to collect prospective data on INFUSE bone graft in posterolateral and transforaminal lumbar interbody fusion. 

Studies suggest that a single injection of Mesoblast’s Mesenchymal Precursor Cells resulted in meaningful improvements in chronic low back pain and function that were durable for at least 3 years. 

SpinalCyte announced the first injection in a clinical trial of CybroCell fibroblasts for spinal disc regeneration. 
 

Trauma

Bone Therapeutics reported positive interim efficacy results and early conclusion of the Phase I/IIA study of ALLOB allogeneic bone cell therapy in the treatment of delayed-union fractures. Given the close relationship between the delayed-union and non-union indications, the company will also cease recruitment in the PREOB non-union trial to focus resources on ALLOB. 

BONESUPPORT enrolled the first patient in the pivotal Investigational Device Exemption trial of CERAMENT G in the surgical repair of open diaphyseal tibial fractures. 

Carmell Therapeutics will launch a Phase III clinical study for Bone Healing Accelerant, its first Plasma-based Bioactive Material product/indication, designed to treat fractures. 

Interim results from study of PolyPid’s BonyPid-1000 bone substitute in the treatment of open tibial fractures indicate that the product met performance and safety endpoints in first patients at 6 months. 
 

Soft Tissue Repair

MiMedx commenced a Phase III study to evaluate AmnioFix Injectable allograft vs. placebo in the treatment of Plantar Fasciitis. 

Orthocell announced recruitment of the first patient in a clinical trial investigating Ortho-ATI to treat rotator cuff tendinopathy. 

Six-month results from Phase I/II study indicate that RepliCel’s RCT-01 fibroblasts demonstrated product safety and clinical potential for tendon regeneration and healing. 

Interim study results indicate that patients receiving Rotation Medical’s Bioinductive Implant to treat rotator cuff disease reported statistically significant improvement at six months. Earlier results indicated inducement of new tissue formation in all study participants with large and massive rotator cuff tears. 
 

Julie A. Vetalice is ORTHOWORLD’s Editorial Assistant. She can be reached by email.