Submission of New Drug Application for Rovatirelin (KPS-0373) for the treatment of Spinocerebellar Degeneration

Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano; Chairman and CEO: Mutsuo Kanzawa) announced that it has submitted a new drug application for marketing approval in Japan for rovatirelin (generic name, development number: KPS-0373), a drug for the treatment of spinocerebellar degeneration.

Rovatirelin was discovered by Shionogi & Co., Ltd. (Headquarters: Osaka; President & CEO: Isao Teshirogi, Ph.D.), and Kissei acquired the development and commercialization rights in Japan from Shionogi and developed it as an agent for spinocerebellar degeneration. Kissei conducted two Phase III clinical trials. Although rovatirelin demonstrated safety and was well-tolerated, no statistically significant improvement was observed in the change in total SARA score to assess for ataxia compared with the placebo group, the primary endpoint, in any of the studies. On the other hand, a pooled analysis (post hoc analysis) of patients who met the inclusion criteria of the second Phase III clinical trial, patients with more severe condition, showed a statistically significant improvement in the change in total SARA score compared with the placebo-treated group^※.

※:J Neurol Neurosurg Psychiatry 2020;91:254-262. doi:10.1136/jnnp-2019-322168

Spinocerebellar degeneration is a generic term for a nerve degeneration disorder of unknown etiology in which symptoms such as ataxia appear owing to the degeneration of the cerebellum or spinal cord. It is a designated intractable disease by the Ministry of Health, Labour and Welfare. While irreversible neuropathy gradually progresses, the therapy of spinocerebellar degeneration is limited to symptomatic treatment, and patient satisfaction and contribution of drug treatment are very low. Based on the results of two previous clinical phase III studies and a pooled analysis, Kissei have judged that rovatirelin is the first drug to be demonstrated for improving the ataxia in spinocerebellar degeneration by the internationally used SARA score, and submitted a new drug application for marketing approval in Japan.

We will make every effort to obtain marketing authorization approval for rovatirelin so that we can provide a new treatment to patients with spinocerebellar degeneration waiting for a new drug.

The milestone payment is trigerred by this event, but it has already been incorporated into the consolidated earnings forecast for the fiscal year ending March 2022 announced on November 9, 2021.



《 Reference 》

About Rovatirelin (generic name, development number: KPS-0373)
Rovatirelin is a derivative of thyrotropin-releasing hormone (TRH) discovered by Shionogi & Co., Ltd. It activates the nervous system by promoting the release of acetylcholine and monoamine neurotransmitters such as dopamine after binding to TRH receptors distributed in the central nervous system, and is expected to improve the ataxias in patients with spinocerebellar degeneration.

In our two phase III clinical trials, no statistically significant improvement was observed in the primary endpoint in any of the trials compared with the placebo group. However, a pooled analysis (a post-hoc analysis) of these two Phase 3 clinical studies in patients who met the inclusion criteria for the second Phase 3 clinical study, patients with more severe condition, showed statistically significant improvements in the total SARA scores compared with placebo (1.03-points improvement in the placebo group and 1.64-points improvement in the rovatirellin 2.4mg group). In addition, the most common adverse events (5% or more) in the rovatirelin group were nasopharyngitis, nausea, weight decreased, and contusion, and most of them were mild in severity. In January 2020, the results of these trials was published in the Journal of Neurology, Neurosurgery, and Psychiatry^※.

※:Nishizawa M, Onodera O, Hirakawa A on behalf of the Rovatirelin Study Group, et al.
　 Effect of rovatirelin in patients with cerebellar ataxia: two randomised double-blind placebo-controlled phase 3 trials.
　 J Neurol Neurosurg Psychiatry 2020;91:254-262. doi:10.1136/jnnp-2019-322168
　 URL:https://jnnp.bmj.com/content/early/2020/01/21/jnnp-2019-322168

About spinocerebellar degeneration
Spinocerebellar degeneration is a nerve degeneration disorder of unknown etiology in which symptoms such as ataxia appear owing to the degeneration of the cerebellum or spinal cord. It is designated as an intractable disease by the Ministry of Health, Labour and Welfare, with 30,000 or more patients certified with this condition in Japan. Although the pathogenesis has been investigated by recent basic research, many aspects remain unclear and there is no definitive treatment. Therefore, symptomatic treatment is currently performed. The "Survey of Medical Needs on Neurologic Diseases" conducted in cooperation with the Japan Health Sciences Foundation and the Japan Society of Neurological Therapeutics reported that spinocerebellar degeneration is a "disease for which development of new therapies is urgent" for the following reasons: low treatment satisfaction, low availability of drugs, and the absence of effective treatment.

About SARA (Scale for the Assessment and Rating of Ataxia)
It is a semi-quantitative method for the assessment of ataxia in spinocerebellar degeneration and other similar conditions; it consists of eight categories (gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide) and is used internationally. The scores from the eight categories are summed, with a maximum score of 40; 0 indicates no symptoms and 40 indicates the most severe symptoms.

In addition, it is believed that caregiving is started to become necessary if SARA score exceeds 15 points.