Bile, which helps digest food, is made in the liver and travels to the intestines. If a gene mutation causes a problem with a protein involved in bile excretion, bile cannot circulate and builds up in the liver, causing it to fail. This is a condition known as progressive familial intrahepatic cholestasis (PFIC).

PFIC has a global prevalence of about one in 100,000 people. It is an extremely rare disease, with an estimated 50 patients in Korea. However, it is a dangerous disease that causes sleep disturbances and growth retardation due to intense itching, and can lead to death if liver function continues to decline without treatment.

For this reason, the government selected the PFIC drug Bylvay (odevixibat) as the first drug to be approved for the “Pilot Project for Approval, Evaluation, and Negotiation Linkage System” in August. It took 10 months, considering the application was submitted in October last year. This is a remarkable achievement, considering it takes at least a year to approve new drugs.

However, it's not a big pharma that has been writing these success stories. It's Ipsen Korea, which professes itself to be a midsize biopharmaceutical company. Ipsen Korea has challenged the Korean rare disease treatment market by focusing on treatments for rare liver diseases, saying, “We will ensure that even a small number of patients are not marginalized and receive the right treatment at the right time.”

Korea Biomedical Review interviewed Shim Jung-hwan, managing director of Ipsen Korea’s Oncology & Rare Disease Business Unit, established in May, to learn about the company's challenges and future blueprint.

Question: Briefly introduce Ipsen Korea’s Oncology & Rare Disease Business Unit.

Answer: Ipsen Korea's Oncology & Rare Disease Business Unit was established in May to provide much-needed therapies to patients suffering from rare diseases. Ipsen is focused on developing innovative treatments for patients with rare diseases and bringing them to Korea. Ipsen Korea's goal is to ensure that even a small number of patients are not marginalized and receive the right treatment at the right time.

Q: What are some of the therapies that have been or will be introduced in Korea?

A: Our current priority area is rare liver diseases. On Aug. 23, we received approval for the rare disease treatment Bylvay. Bylvay is approved for treating pruritus in a rare genetic disease called progressive familial intrahepatic cholestasis (PFIC) and is indicated for use in infants over three months of age. There are only about 50 PFIC patients in Korea, making it an extremely rare disease.

In addition to PFIC, Bylvay is conducting clinical trials for three other cholestatic liver diseases, including Alagille syndrome and biliary atresia, and plans to apply for approval to expand the indications.

The company also seeks approval for elafibranor to treat primary biliary cirrhosis/cholangitis (PBC), a rare liver disease. Elafibranor was designated as an orphan drug in Korea in June. The prevalence of PBC in Korea is reported to be 4,230 patients in the 2009-2019 PBC epidemiologic study.

PBC is characterized by the progressive destruction of bile ducts inside the liver, which can lead to liver failure if left untreated. The risk of death cannot be ruled out. For example, patients who respond to ursodeoxycholic acid (UDCA) treatment and do not develop cirrhosis have a favorable prognosis. However, if they do not respond to UDCA and develop cirrhosis, liver transplantation is the only treatment option. There is no approved treatment for PBC that does not respond to UDCA in Korea.

In addition, the company is considering launching a treatment for advanced ossifying fibrous dysplasia (Fibrodysplasia ossificans progressive, or FOP).

In July, the company acquired the rights to a drug called tovorafenib for treating low-grade glioma in children from another company and is also considering launching it in Korea. Glioma is a type of brain cancer that recently came to the public's attention when the husband of actress Kim Jung-hwa was diagnosed with low-grade glioma.

Q: What kind of treatment is Bylvay?

A: Bylvay is a drug that works by the mechanism of ileal bile acid transporter (IBAT) inhibitors, which help release bile from the liver without accumulating. If treated properly at an early age, it can ultimately prevent the destruction of the liver from fibrosis. However, if the condition is so severe that it is likely to lead to cirrhosis or liver cancer, even newborns under one year of age should receive a liver transplant. Medical professionals hope that these children will survive until they are old enough to receive a liver transplant. So, doctors’ expectations are high.

Q: When does PFIC disease start?

A: The most common subtypes, PFIC Types 1 and 2, usually appear in infancy and early childhood, but some of the less common subtypes can appear in adolescence or adulthood. Symptoms of the disease include intense itching. Patients scratch until they bleed. It can be confused with atopy and can cause sleepless nights for both children and parents. This is why growth is stunted. The liver is constantly failing, leading to the need for a transplant.

Q: How many people are affected by PFIC worldwide?

A: As with any rare disease, it's difficult to determine the exact number of patients. The exact prevalence of PFIC is unknown, but it affects a very small number of people. It is estimated to be one in 50,000 to 100,000 people worldwide.

Q: How long has Bylvay been on the market?

A: Bylvay was developed by a pharmaceutical company called Albireo, which Ipsen acquired in 2023. It was licensed in the United States, Europe, and other countries in 2021. It has been in Korea for three years, so it's never too late. It was the first drug to be licensed in Asia thanks to the government’s pilot project for approval-evaluation-negotiation linkage system.”

Q: Besides rare liver diseases and glioma, what other treatments are you considering introducing (licensing)?

A: We are expanding indications for our already launched products through ongoing global clinical trials. For example, our anticancer drug Cabometyx is mainly used for kidney cancer, but it also has indications for liver and thyroid cancer, and we are preparing to license it for neuroendocrine tumors. The results of phase 3 were recently presented at ESMO, and the patient's association has contacted us.

Q: Ipsen's business strategy targets rare diseases with a small number of patients.

A: On its website, Ipsen emphasizes that it is a “midsized biopharmaceutical company leading the market.” Rather than focusing on developing treatments for diseases with many patients like big pharma, Ipsen's goal and strategy is to provide innovative treatments for patients who need them, even if they are few.

Q: It takes a long time for new rare disease treatments to be introduced in Korea.

A: We know it takes about one year for approval and an average of two years to receive reimbursement for new drugs for rare diseases in Korea. This is because each process requires review and consultation on important and demanding items, such as safety, efficacy, quality, GMP, clinical utility, and cost-effectiveness.

The Ministry of Health and Welfare has also recognized the problem of speeding up access to new drugs and is conducting a parallel approval, evaluation, and negotiation pilot project. Ipsen's Bylvay is being evaluated as the first pilot project. It would be great if it could be widely expanded. At Ipsen, we are also making various efforts to quickly provide the first treatment to marginalized PFIC patients.

Q: Have you encountered any challenges in the approval or reimbursement process?

A: The biggest challenge for Ipsen and other pharmaceutical companies with a rare disease division is access to new drugs. For extremely rare diseases like PFIC, where there are only a few dozen patients in the country, there are no internationally accepted guidelines, few patients enrolled in clinical trials, and minimal clinical evidence, including real-world data or sub-analyses. If these characteristics of rare diseases are not considered and indications and reimbursement criteria are evaluated according to the same criteria as generic drugs, the minority of patients with rare diseases will continue to have limited access to new drugs. Therefore, there is a need for a reimbursement system tailored to the specific needs of rare diseases.

Q: What has been rewarding about leading the rare diseases business unit at Ipsen?

A: Ipsen's acquisition of Albireo last year was rewarded with the first Asian approval of Bylvay in August. It takes a fast-moving group of people to get approval so quickly for a company that is not big.

I think agility allowed us to move things along so quickly. Being a relatively small company with a clear vision and philosophy of “becoming a leading midsized company,” I think we could execute new strategies quickly and respond to changes.

It's also very rewarding to make a small contribution to rare diseases that are underserved and the doctors who treat them. We are working with like-minded people in our unit to improve the treatment environment with a sense of mission.

Q: Many pharmaceutical companies are engaging in CSR activities to improve the quality of life for patients with rare diseases. What is Ipsen doing in this regard?

A: We are about to begin. PFIC is an extremely rare disease with no cure, so there are no patient organizations. We are working closely with the Korean Organization for Rare Diseases (KORD), and if a PFIC patient group is created, we would like to consider raising awareness of the disease and improving patients' quality of life.

Patients with PFIC, Alagille syndrome, and primary biliary cholangitis (PBC) don't have a clear channel of where to go and what to ask. We want to create an opportunity to provide support centered around KORD.

Q: Explain the diseases Ipsen focuses on and any initiatives your business unit focuses on to improve the treatment landscape for targeted rare diseases it plans to develop.

A: Our rare disease business unit is focused on rare liver diseases. We want to create an environment where patients have unrestricted access to all treatments soon. It is difficult to share specific plans, but we are preparing various educational programs for relevant societies and medical staff.

Q: Any messages for patients and the public?

A: Ipsen may not be a household name, but it has existed for nearly 100 years. Ipsen has many innovative therapies in cancer, rare diseases, and neuroscience, so I would like to make Ipsen more known. We are very serious about rare liver diseases, and we will do our best to get them approved as quickly as possible through government pilot programs so that they can get reimbursed quickly.