“There are over 10,000 rare diseases but how many of them have a cure?” When I introduce the diagnosis of rare diseases, I often get questions about treatment. I tend to give the general answer that therapies are being developed for about 5 percent of rare diseases, and there is no cure for 95 percent of rare diseases. I also reply that treatment of a disease includes not only drugs but surgery, therapies other than drugs, and diet control and that an accurate diagnosis is important. Then, I would add, as hundreds of rare disease treatments are currently in clinical trials, the number of rare disease treatments will increase sharply in the future.

The development of orphan drugs has been slow because they target a small number of patients. Hurdles include the issue of medical utility, economic feasibility, and difficulties in enrolling patients for clinical trials. To address this problem, the U.S. government enacted the Orphan Drug Act (ODA) in 1983 and started giving various benefits to companies for the development of orphan drugs. Since then, the number of FDA-registered orphan drugs receiving ODA benefits has reached 6,421 as of September 2022, and orphan drug development is very active in the U.S.

With regulatory support such as ODA, the clinical trial period of an orphan drug is nine months shorter than that of a non-orphan drug on average, and the FDA approval is about eight months faster. An orphan drug developer gets tax benefits for the development cost, too. Still, it is too much to say that the benefits of the process of a new drug development accelerated orphan drug development. Considering an astronomical cost of new drug development, a little shorter development period and a slight reduction of cost are not sufficiently attractive for a pharmaceutical firm to jump into orphan drug development.

Only when a pharmaceutical company can recover drug development costs and see an economic utility high enough to make a profit, it can actively develop an orphan drug. Global sales of orphan drugs are expected to reach 240 trillion won ($168.2 million) in 2022 and continue to grow by 12 percent annually in the future to account for more than 20 percent of the total pharmaceutical market. At Johnson & Jones, the world's No. 1 pharmaceutical company, sales of orphan drugs took up 25 percent of the total revenue in 2021. This proportion is expected to increase to 39 percent in 2026. During the same period, at AstraZeneca, the second-largest by sales, the proportion of orphan drugs is expected to go up from 19 percent to 36 percent. At Roche, the third-largest, the proportion will expand from 21 percent to 26 percent.

This proves that orphan drugs, which were thought to be uneconomical for a small number of patients, actually grow into new blockbuster drugs that generate billions of dollars in sales per year. Vertex developed Trikafta, a treatment for cystic fibrosis, a rare disease that occurs in an average of one in 9,000 people. Trikafta’s annual revenue reached approximately $5.69 billion in 2021. Sanofi-Genzyme developed Fabrazyme, a treatment for Fabry disease, a rare disease that occurs in an average of 1 in 15,000 people. This orphan drug is generating about $700 million in annual sales in 2021.

Orphan drugs without a rival medicine can monopolize the global market, and the cost savings are reflected in the price, which makes the drug price expensive. Reflecting this aspect, an environment is available for orphan drugs to become new blockbuster drugs. As people saw examples of orphan drugs proving economically viable, these examples prompted more pharmaceutical firms to join the race to develop orphan drugs.

The development of orphan drugs is expected to accelerate going forward. Every year, about 400-500 new orphan drugs are registered as ODA drugs for clinical trials. The emergence of genetic therapeutics and AI-backed drug development technology will speed up the development of pipelines for orphan drugs.

Korean companies are also actively working on orphan drugs. Korean firms’ orphan drugs registered as ODA drugs at the FDA reached 69. As of 2021, 14 investigational orphan drugs are being developed in Korea. Among them, no drug has passed clinical trials and won approval. The jittery global financial markets are making it difficult for new drug developers to raise additional funds for clinical trials. I hope Korean orphan drug developers could overcome the tough times, succeed in commercializing those drugs, and give hope to rare disease patients worldwide.

This column was originally published in Korean in Korea Healthlog. -- Ed.