CYBERDYNE Inc. (Tsukuba, Ibaraki; President & CEO: Yoshiyuki Sankai, the “Company”) announced today that the application submitted on August 24, 2021, to expand the approval for Medical HAL to treat HTLV-1-related myelopathy (from now on “HAM”) (*1) and hereditary spastic paraplegia (*2) in addition to previously approved indications were accepted.

The Company used the result of an investigator-initiated clinical trial led by Dr. Takashi Nakajima (Director of National Hospital Organization Niigata Hospital) supported by the Japan Agency for Medical Research and Development (AMED). The clinical trial was titled “Investigator-Initiated Clinical Study of Wearable Assistive Robot for Lower Limbs Controlled Voluntarily by Bioelectric Signals etc., (Hybrid Assistive Limb [HAL]-HN01) as a New Medical Device to Delay Progression of Intractable Rare Neuromuscular Diseases -A Multicenter Randomized Controlled Parallel-Group Study to Evaluate the Short-Term Gait Improvement Effect on Ambulation Disability Caused by Spastic Paraplegia such as HTLV-1-Associated Myelopathy (HAM), etc.-(STUDY NCY-2001R).”

In Japan, Medical HAL has already been approved for eight types of neuromuscular diseases (*3), such as ALS. With this approval for the additional indications of HAM and hereditary spastic paraplegia, it is expected to be established as a standard treatment to improve gait instability and functional disability caused by progressive intractable diseases for which effective treatments have not been established. The Company will proceed with the procedures to obtain insurance coverage so that medical reimbursement can be calculated by each hospital when they treat HAM and hereditary spastic paraplegia patients with the Medical HAL.

＜Comment from Dr. Takashi Nakajima National Hospital Organization Niigata Hospital＞
HAM is an intractable disease that causes progressive gait disturbance, and the development of treatment has been awaited in regions where HTLV-1 virus carriers are distributed, such as Japan, the Caribbean, countries, South America, Africa, South India, Iran, European countries, and the United States. The success of the NCY-2001 study in Japan, the first study in the world to verify the effectiveness of HAL for improving gait in HAM, is a milestone and has received high praise and surprise from medical specialists worldwide. Furthermore, the fact that the indication has been officially extended to Japan for the first time is expected to make it a standard treatment in the world in the future, and we believe that this will be an important contribution from Japan to the world in economic and humanitarian terms.
The NCY-3001 study had previously demonstrated that the Medical HAL improved gait in patients with lesions in the motor unit (spinal motoneurons and muscle fibers connected to the motor unit) in eight progressive neuromuscular diseases, and now the NCY-3001 study has demonstrated that the Medical HAL significantly improved gait (in the primary and clinically important secondary endpoints) in HAM and hereditary spastic paraplegia, diseases that cause progressive spastic paraplegia due to central nerve lesions above the motor unit. The NCY-2001 study demonstrated that HAL significantly improved gait (in the primary endpoint and clinically important secondary endpoints) over conventional walking exercise therapy in HAM and hereditary spastic paraplegia, conditions that result in progressive spastic paraplegia due to central nervous system lesions above the motor unit. The success of these two trials demonstrated that Cybernics Treatment can regenerate neural function through interactive biofeedback (iBF) regardless of the lesion site, i.e., whether the lesion is in the motor unit or above it, and that it is medically applicable to HF. The results of the NCY-2001 study have been well received by the review authorities, and we believe that the results will encourage further expansion of the indication in the future.

＜About the NCY2001 Study＞
The study hypothesized that “the progression of diseases such as gait instability could slow down when Medical HAL Lower Limb Type (from now on referred to as “HAL-HN01”) is worn therapeutically on a regular and intermittent basis for appropriate muscle contraction.” Therefore, this investigator-led clinical trial aimed to evaluate the efficacy and safety of HAL-HN01, including its effect on improving patient gait.

・Primary efficacy endpoint: 2-minute walk test (indicates distance and walking endurance)
・Secondary endpoints: 10-meter walk test (speed), the patient-reported outcome measure (PRO), gait assessment by health care providers, barn motor disability severity (OMDS), spasticity (Modified Ashworth scale (MAS) assessment, SCATS Clonus scale, manual muscle testing (MMT), ADL assessment (Barthel index), operator’s assessment of HAL-HN01 use.

(Reference) Japan Medical Association Clinical Trial Promotion Center’s Clinical Trial Registration System JMACCT ID：JMA-IIA00257
https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=5969

This study is a part of the “Practical Application Research Project for Intractable Diseases” funded by Grant-in-Aid for Scientific Research from Ministry of Health, Labour and Welfare (FY 2012-2014), “Investigator-Initiated Clinical Study of Wearable Assistive Robot for Lower Limbs Controlled Voluntarily by Bioelectric Signals etc., (Hybrid Assistive Limb [HAL]-HN01) as a New Medical Device to Delay Progression of Intractable Rare Neuromuscular Diseases” (Principal Investigator: Takashi Nakajima), and a part of the research funded by the Japan Agency for Medical Research and Development (hereinafter referred to as AMED) from FY2007 to FY2008, ” Multicenter clinical trials on efficacy and safety of cybernic treatment using cyborg-type robot HAL-HNO1 for the patients with gait dysfunction due to rare/intractable brain & spinal cord diseases ” (Principal Investigator: Takashi Nakajima).
The study was conducted at the National Hospital Organization Niigata Hospital, St. Marianna University Hospital, Kyoto Prefectural University of Medicine Hospital, Fukuoka University Hospital, National Hospital Organization Tokushima Hospital, University of Tsukuba Hospital, Kagoshima University Hospital, Kirishima Rehabilitation Center, and National Hospital Organization Murayama Medical Center as an investigator-initiated clinical trial. The research was conducted at the National Hospital Organization Murayama Medical Center. The Company participated as a research partner of the Grant-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare, and also as a research and development entrusted by the National Hospital Organization Niigata Hospital (Principal Investigator: Takashi Nakajima) based on a contract research and development agreement signed by the National Hospital Organization Niigata Hospital and AMED as of April 1, 2017.

*1 HTLV-1-associated myelopathy (HAM):
It is a rare disease, with an estimated 3,000 patients nationwide, and it is one of the designated intractable diseases. It is an intractable disease that progressively damages the spinal cord, causing symptoms such as difficulty in walking, urination, defecation, numbness, and pain in the legs. The condition eventually forces patients to live in wheelchairs or bedridden, leading to a severe decline in quality of life.

*2 Hereditary spastic paraplegia:
It is a rare genetic disorder that causes gradual muscle weakness with spasticity in the legs and is one of the designated intractable diseases. It can occur at any age and causes excessive reflexes, spasticity, and paralysis, making walking difficult.

*3 Progressive neuromuscular incurable diseases (8 diseases):
Spinal muscular atrophy (SMA), Spherospinal muscular atrophy (SBMA), Amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease, Distal myopathy, Inclusion body myositis, Congenital myopathy, Muscular dystrophy.