■Overview and progress of major development pipelines

3. emixstat hydrochloride

Stargard disease is a genetic disorder of the retina, and poor eyesight and color vision impairment from childhood to adolescence are the main symptoms. Also known as juvenile macular degeneration, it is estimated that there are less than 150,000 patients in Europe, America, and Japan*1, and the incidence rate is 1 rare disease in 80 to 10,000 people. Most patients are said to have reduced eyesight to 0.1 or less, and it is one of the diseases with strong unmet medical needs for which an effective treatment has not yet been established, and emixstat hydrochloride (hereafter, emixstat) is designated as an orphan drug in the United States. There is also an investigation report*2 showing that the market size of Stargard disease will be approximately 230 billion yen (1 US dollar = 145 yen equivalent) in 2027, and Kubota Pharmaceutical Holdings ＜4596＞ has determined that development significance is significant.

*1 Market Scope, 2015 Report on the Retinal Pharmaceuticals & Biologics Market; UN World Population Assessment 2015

*2 WISEGUY RESEARCH CONSULTANTS PVT LTD Global Juvenile Degenile (Stargardt Disease) Market Research Report- Forecast to 2027

The company announced the results of the Phase 3 clinical trial (194 subjects) in 2022. As an abstract, since no statistically significant differences were obtained with respect to the placebo group in the main evaluation items and secondary evaluation items, it was not possible to apply for approval, but as a result of performing detailed data analysis, the content suggests that there is a significant difference when viewed only by patients in the initial symptom stage, ※, so we are proceeding with a review of development strategies. Since it is difficult to conduct clinical trials alone due to the current financial situation, preparations are currently underway to discuss with PMDA ((Germany) Pharmaceuticals and Medical Devices Organization) whether it is possible to carry out manufacturing and sales approval applications utilizing early approval systems, etc. including Japan. The pioneering drug designation system was revised in Japan in 2023/12, and it is now possible to use data from clinical trials conducted overseas for data such as clinical trials required for approval applications. Since safety and tolerability have already been confirmed, we believe that there is a possibility that it will be approved if it is designated as a pioneering drug and can be applied for.

* According to the results of all case data, the progression rate of macular atrophy, which is the main evaluation item, was 1.280 square mm/year in the emixstat administration group and 1.309 square mm/year in the placebo group, and no significant difference was obtained (p=0.8091). However, as a result of subsequent data analysis, it was suggested that, when limited to the group of subjects with a smaller atrophy lesion area at baseline, the macular atrophy progression rate in the 24th month of the emixstat administration group was drastically suppressed to 40.8% compared to the placebo group, and there was a significant difference (P = 0.0206, emixstat administration group n = 34, placebo group n = 21). The reason why the sample number of initial symptoms was small was that the target age of subjects was 16 years old or older.

When applying for manufacturing and sales approval, it becomes necessary to decide whether to carry out sales in-house or by concluding a sales partner agreement. This is because when sales are carried out in-house, it is necessary to establish a system for the three regulatory affairs actors (general manufacturing and sales manager, quality assurance officer, safety management officer) before applying for approval, and it is also necessary to establish a logistics system, etc. Meanwhile, if a sales partner agreement is concluded, most of such system development can be outsourced to a partner. We believe that it is ideal if a partner agreement can be concluded with a pharmaceutical company that is likely to become a sales partner even overseas, since such cost burdens will also be reduced. In any case, it is expected that the direction will be decided within 2024, and this trend is attracting attention.

(Author: FISCO Visiting Analyst Joe Sato)