Notice of publication of a newspaper article in Kahoku Shimpo regarding malignant melanoma treatment drug

In collaboration with medical institutions and research institutes such as Tohoku University, we are developing the PAI-1 inhibitor RS5614 for the treatment for malignant melanoma. We are pleased to announce that a newspaper article about Associate Professor Taku Fujimura at the Department of Dermatology, Graduate School of Medicine, Tohoku University, who conducted the phase II trial as a coordinating physician, has been published in the Kahoku Shimpo (August 31, 2024 issue). 

[Article link] 

Malignant melanoma is a rare cancer in which cells that produce melanin pigment become malignant, causing black tumors to form on the skin of the hands and feet. As the disease progresses, the mortality rate is high, and it is said that there are approximately 5,000 patients in Japan. Immune checkpoint inhibitors^*1 such as nivolumab (Opdivo)^*2 are used as treatment drugs, but only about 20% of Japanese patients are effective. 

In collaboration with six medical institutions including Tohoku University hospital, we conducted the Phase II trial of RS5614 in combination with nivolumab from September 2021 to March 2023 with patients with malignant melanoma for whom nivolumab is ineffective. The drug was administered to 39 patients for two months and, of note, the symptoms of more than half of the patients did not worsen for six months, and the effects of nivolumab continued even after the end of administration. While approximately 60% of patients experienced serious side effects when using conventional medications (a combination of nivolumab and ipilimumab^*6), the rate was 7.7% with our combination with RS5614, making it highly safe. 

Based on these promising results of the Phase II trial, we plan to conduct a Phase III trials this year. In addition, we received an orphan drug designation^*4 from the Ministry of Health, Labor and Welfare on August 28, 2024, and are proceeding with development toward the regulatory approval. 

^*1 Immune checkpoint inhibitors 
A group of molecules that inhibit immune responses against oneself and suppress excessive immune responses in order to maintain immune homeostasis. Immune checkpoint molecules exist to suppress excessive activation of lymphocytes and prevent them from attacking themselves, but cancer cells abuse immune checkpoint molecules to avoid attacks from the immune system. Currently, various immune checkpoint molecules such as PD-1 and CTLA-4 have been identified. Immune checkpoint molecule inhibitors are antibody drugs that inhibit these molecules and normalize the cancer immunity. 

^*2Nivolumab 
An antibody drug (human anti-human PD-1 monoclonal antibody) that targets the immune checkpoint molecule programmed cell death 1 (PD-1), it is a drug that aims to have an anti-cancer effect by releasing the inhibition of the immune system. It is a representative immune checkpoint inhibitor. In Japan, the response rate of nivolumab for malignant melanoma is 22.2%, and the development of new combination therapies is desired. 

^*3 Nivolumab/ipilimumab combination 
In a Phase III multicenter clinical trial targeting untreated advanced or recurrent non-small cell lung cancer, deaths for which a causal relationship to treatment could not be denied occurred in approximately 7.4% (11 of 148 patients), exceeding the expected range, in patients who received the immune checkpoint inhibitor combination therapy of nivolumab/ipilimumab. The trial was discontinued on March 30, 2023. 

^*4Designation as an orphan disease drug 
A drug for orphan diseases with few patients and no established treatment, such as intractable diseases. There are designation criteria such as the number of target patients being less than 50,000, targeting serious diseases such as intractable diseases, high medical need, no suitable alternative drugs or treatments, expected to be significantly more effective or safe than existing drugs, and high possibility of development. When designated as an orphan disease drug, it will be subject to priority review by the Pharmaceuticals and Medical Devices Agency (PMDA) (shortening the review period), a marketability surcharge in drug price calculation, and an extension of the reexamination period after approval, resulting in a longer monopoly period for this treatment drug business. In addition, there are preferential treatment measures such as subsidies through the National Institutes of Biomedical Innovation, Health and Nutrition.