SAWC Spotlight: Amniox Discusses Company Developments

We are witnessing an explosive growth of the human birth tissue industry, which now has reached $1 billion annually according to primary market research from Health Advances and third party sources. How is Amniox contributing to this growth?

Amniox, and its parent company TissueTech, have pioneered the study of the natural healing elements of human birth tissue for more than 30 years. Our mission is to address unmet clinical needs as the patient-focused pioneer of birth tissue regenerative medicine and the evidence-based market leader in ocular, surgical wound, and pain management markets. Rooted in its mission, Amniox provides differentiated, customer-recognizable, and sustainable health economic value.

Our primary goal is to be the industry leader in birth tissue regenerative medicine—driving our transition from a leader in the tissue space to an emerging biotech company.

How is Amniox leading the way in this transition?

We have been diligent in building an infrastructure to develop products as biologics under Section 351 of the Public Health Service Act, pursuing the Biologics License Application (BLA) regulatory pathway for several years now. Our parent company, TissueTech, has invested heavily in growing internal capabilities with the expansion of the clinical organization and the addition of a technical operations group to support technology transfer. We determined early on that going after BLA approval in target indications such as wound care would be the right thing to do, as evidenced by the success of our clinical studies.

We initiated the first of two Phase 3 clinical trials in July 2020 using TTAX01 (an investigational Cryopreserved Umbilical Cord [CUC] birth tissue allograft) to treat complex Wagner grades 3 and 4 diabetic foot ulcers (DFUs). These DFUs presented with evidence of exposed bone, tendon, muscle, and/or joint capsule as well as clinical suspicion of osteomyelitis or evidence of bone necrosis. Thus, TTAX01 holds the distinction of being the first birth tissue product to seek U.S. Food and Drug Administration (FDA) approval as a biologic for the treatment of complex Wagner grade 3 and 4 DFUs.

Results from a one-year follow-up study to our Phase 2 clinical trial using TTAX01 to treat complex, non-healing DFUs indicated that TTAX01 is a promising therapy with a higher healing rate than the standard of care for the management of advanced DFUs complicated by osteomyelitis.¹ Investigators found that 86.2% of patients achieved complete wound closure with TTAX01.¹ This percentage is significantly higher than the U.S. Wound Registry’s reported rate of 45% healing of all DFUs regardless of treatment time.² These results are comparable to previously reported results using the commercially available CUC NEOX in a retrospective study.³

TTAX01 is still an Investigational New Drug (IND), correct? Do you have products currently on the market to help patients with complex DFUs who may be facing the risk of a lower limb amputation if their wounds do not close?

Amniox’s commercially available 361 Human Cellular Tissue Product, CUC NEOX, performed similarly to TTAX01 in a retrospective case series, showing an overall healing rate of 87.5%. The average time to wound closure was 13.8 ± 1.95 weeks, with a median of 9 weeks and an average of 1.68 ± 0.18 CUC applications.¹

These results suggest that CUC NEOX is effective in supporting improved healing of DFUs as well as potentially reducing the medical costs associated with chronic DFUs due to the low number of applications needed to achieve complete wound closure. CUC NEOX has demonstrated the potential to improve patient quality of life and positively impact rising healthcare costs associated with long-term treatment of such ulcers.^4-8 When used as an adjunct therapy, CUC NEOX has been shown to help accelerate wound healing, minimize the risk of infection or amputation, and support complete epithelization.^5-15

What is on the horizon of product development at Amniox and TissueTech?

We recognized the therapeutic benefits of using birth tissue early on to address severe diseases for which there are unmet clinical needs. Our Cryopreserved Amniotic Membrane and Umbilical Cord birth tissue allografts inherently contain a unique extracellular matrix that exerts anti-inflammatory, anti-scarring, and pro-regenerative effects.¹⁹ These characteristics make our birth tissue allografts an ideal treatment option to promote closure of hard-to-heal complex wounds, as evidenced by published study results.

The FDA also granted TissueTech a Regenerative Medicine Advanced Therapy designation for IND TTAX02 for the treatment of spina bifida in utero. As a result, we are also embarking on an additional IND program to launch a Phase 3 trial in fetal surgery of spina bifida. This rare pediatric disease manifests as a failure of the caudal neural tube to fuse naturally in early development, resulting in the lack of complete closure of the spinal vertebral column around the developing spinal cord. Depending on the location and extent of spinal cord involvement, these patients may experience mild to severe life-long disabilities.

Most recently, Yun Guan, MD, PhD, professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine, was awarded a 5-year R01 grant from the National Institutes of Health. His preliminary data suggested that these tissue products play a key role by suppressing the inflammatory response while also directly inhibiting the excitation of nerve cells that cause pain. The study, “Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain,” will be conducted in collaboration with TissueTech. We are very proud to support this initiative and work diligently with research partners to combat opioid misuse. Opioid misuse has devastating consequences as illustrated by the fact that roughly 21% to 29% of patients who are prescribed opioids for chronic pain misuse them.¹⁷

Our clinical activities focus on treating severe conditions that affect patients, ranging from the smallest and most vulnerable pediatric populations in utero to those faced with prevalent complications of diabetes (eg, DFUs). DFUs are the most common underlying cause of non-traumatic, lower-extremity amputations. Looking forward, we see opportunities in wound healing, pain management, and sports medicine for orthopedic surgeons, podiatrists, urologists, plastic surgeons, and gynecologists. Ultimately, we will focus on indications for which we can best improve outcomes and facilitate the treatment of unmet clinical needs.

References

1. Marston WA, Lantis JC, Wu SC, et al. One‐year safety, healing and amputation rates of Wagner 3‐4 diabetic foot ulcers treated with cryopreserved umbilical cord (TTAX01). Wound Rep Reg. 2020;28(4):1–6. doi:10.1111/wrr.12809

2. Fife CE, Eckert KA, Carter MJ. Publicly reported wound healing rates: the fantasy and the reality. Adv Wound Care (New Rochelle). 2018;7(3):77–94. doi:10.1089/wound.2017.0743

3. Caputo WJ, Vaquero C, Monterosa A, et al. A retrospective study of cryopreserved umbilical cord as an adjunctive therapy to promote the healing of chronic, complex foot ulcers with underlying osteomyelitis. Wound Repair Regen. 2016;24(5):885–893. doi:10.1111/wrr.12456

4. Marston WA, Lantis JC, Wu SC, et al. An open-label trial of cryopreserved human umbilical cord in the treatment of complex diabetic foot ulcers complicated by osteomyelitis. Wound Repair Regen. 2019;27(6):680–686. doi:10.1111/wrr.127542

5. Raphael A. A single-centre, retrospective study of cryopreserved umbilical cord/amniotic membrane tissue for the treatment of diabetic foot ulcers. J Wound Care. 2016;25(Sup7): S10–S17. doi:10.12968/jowc.2016.25.Sup7.S10

6. Couture M. A single-center, retrospective study of cryopreserved umbilical cord for wound healing in patients suffering from chronic wounds of the foot and ankle. Wounds. 2016;28(7):217–225.

7. Tseng SC, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocul Surf. 2004;2(3):177–187. doi:10.1016/s1542-0124(12)70059-9

8. Brown NJ, David M, Cuttle L, Kimble RM, Rodger S, Higashi H. Cost-effectiveness of a nonpharmacological intervention in pediatric burn care. Value Health. 2015;18(5):631–637. doi:10.1016/j.jval.2015.04.011

9. Swan J. Use of cryopreserved, particulate human amniotic membrane and umbilical cord (AM/UC) tissue: a case series study for application in the healing of chronic wounds. Surg Technol Int. 2014;25:73–78.

10. Raphael A, Gonzales J. Use of cryopreserved umbilical cord with negative pressure wound therapy for complex diabetic ulcers with osteomyelitis. J Wound Care. 2017;26(Sup10): S38–S44. doi:10.12968/jowc.2017.26.Sup10.S38

11. Bemenderfer TB, Anderson RB, Odum SM, Davis WH. Effects of cryopreserved amniotic membrane-umbilical cord allograft on total ankle arthroplasty wound healing. J Foot Ankle Surg. 2019;58(1):97–102. doi:10.1053/j.jfas.2018.08.014

12. DeMill SL, Granata JD, McAlister JE, Berlet GC, Hyer CF. Safety analysis of cryopreserved amniotic membrane/umbilical cord tissue in foot and ankle surgery: a consecutive case series of 124 patients. Surg Technol Int. 2014;25:257–261.

13. Ellington JK, Ferguson CM. The use of amniotic membrane/umbilical cord in first metatarsophalangeal joint cheilectomy: a comparative bilateral case study. Surg Technol Int. 2014;25:63–67.

14. Garras DN, Scott RT. Plantar fasciitis treatment with particulated human amniotic membrane. Foot Ankle Orthop. 2016;1(1). doi:10.1177/2473011416S00245

15. Hanselman AE, Tidwell JE, Santrock RD. Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study. Foot Ankle Int. 2015;36(2):151–158. doi:10.1177/1071100714552824

16. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569–576. doi:10.1097/01.j.pain.0000460357.01998.f1

17. Stewart CM. The use of cryopreserved umbilical cord in open reduction and internal fixation of calcaneus fractures. SunKrist J Trauma Emerg Med Acute Care. 2019;1(1):1–6.