Promising Rare Diseases in the Korean Market 2: Expanding Regimen in Unmet Needs

In this second part, I will share a detailed overview based on insights I provided during external consulting engagements. We will focus on other critical areas of unmet needs within the Korean rare disease landscape, specifically Hereditary Angioedema (HAE), Hereditary Transthyretin Amyloidosis (hATTR), and Gaucher Disease. These conditions, which have historically been underserved, are now the focus of innovative treatment strategies aimed at addressing significant unmet needs. This article explores the current landscape and future prospects for these conditions in Korea, highlighting the potential for improved patient outcomes and quality of life.

Hereditary Angioedema (HAE)

Initially, the Korean HAE market had about 60 patients who depended on androgen-based replacement therapies, leading to a market that was not well-established. Existing C1 inhibitors like CSL Behring's 'Berinert' and Pharming Group's 'Ruconest' did not receive P&R approval and thus were not launched. Takeda's 'Firazyr' (icatibant) eventually got P&R approval after four years of effort, establishing a market presence and increasing the diagnosis rate from 6% to 30% over three years. This success highlighted the need for more treatment options.

In Korea, HAE management has traditionally relied on acute treatments like CSL Behring's 'Berinert' (C1-inhibitor concentrate) and Takeda's 'Firazyr' (icatibant), with only 'Firazyr' being available commercially. These treatments work for acute episodes but do not prevent future attacks. Recently, preventive therapies have gained attention, with Takeda's 'lanadelumab' ('Takhzyro') emerging as a notable addition. 'Lanadelumab' is a monoclonal antibody given subcutaneously, offering patients the convenience of self-administration and significantly reducing attack frequency.

This shift towards preventive care is expected to improve patient quality of life and reduce healthcare costs related to emergency treatments. However, it has not yet received P&R approval in Korea, with pricing and life-threatening disease considerations being key issues. Additionally, BioCryst Pharmaceuticals' 'Orladeyo' (berotralstat) is exploring market entry following these developments.

Beyond preventive therapies, researchers are looking into small molecule drugs targeting the kallikrein-kinin pathway, which could offer more targeted and long-term management of HAE. Pharvaris is developing 'PHVS416', an oral bradykinin B2 receptor antagonist, currently in clinical trials. KalVista Pharmaceuticals is working on pipeline products like 'KVD900', an oral on-demand treatment for HAE attacks, and 'KVD824', a potential oral prophylactic treatment. CSL Behring is optimistic about expanding its HAE portfolio, offering 'Haegarda', a C1-esterase inhibitor for subcutaneous prophylaxis, and exploring new therapies to enhance patient care.

From an insurance perspective, only on-demand treatment options are currently available, with monthly prescription limits, highlighting the need for alternative treatment options. The introduction of preventive therapies in Korea represents a major shift in HAE management, emphasizing the importance of long-term disease control over acute intervention. This shift is likely to increase demand for innovative therapies and encourage further investment in HAE research and development.

Hereditary Transthyretin Amyloidosis (hATTR)

In Korea, Hereditary Transthyretin Amyloidosis (hATTR) is mainly treated with Pfizer's 'tafamidis' ('Vyndaqel'), which targets cardiomyopathy associated with the disease. This oral medication stabilizes the transthyretin protein, slowing disease progression. RNA-based therapies such as Alnylam Pharmaceuticals' 'patisiran' ('Onpattro') and Ionis Pharmaceuticals' 'inotersen' ('Tegsedi') are actively researched and expected to enter the Korean market soon.

These therapies have shown promise in reducing amyloid deposits and improving clinical outcomes by targeting the disease at a genetic level. Efforts are underway to develop treatments that can cross the blood-brain barrier (BBB), addressing the neurological symptoms of hATTR.

Alnylam’s 'Amvuttra' (vutrisiran), with its unique RNAi mechanism of action, is expected to enter the Korean market next and will be marketed by Medison Pharma. Medison Pharma is recognized for its effective market access strategies, which focus on quickly delivering breakthrough therapies to patients. Their approach includes strategic partnerships and utilizing local expertise to navigate regulatory landscapes. This model is expected to facilitate the successful introduction of 'Amvuttra' in Korea, ensuring that patients have timely access to this advanced treatment option.

Currently, no approved drugs are available for ATTR-CM in the market, as no treatments have received regulatory approval or pricing agreements. However, Pfizer’s 'Vyndaqel' has been approved for the indication and is awaiting pricing negotiations. Significant progress has been made since 2021, and there is growing optimism about approval. Once launched, approximately 200 echocardiography specialists will become the target customer base. It is estimated that around 100-150 patients have been diagnosed, assuming a prevalence of 500-1,000 patients in the population.

This translates to a diagnosis rate of approximately 10%-15%. While this rate is lower than international averages, the primary limitation lies in the lack of reimbursement for treatment. Given Korea’s advanced healthcare system and specialized market expertise in rare diseases, the diagnosis rate is expected to improve with effective market entry strategies. 'Vyndaqel' is approved for the treatment of hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN). 'Vyndamax' is currently under consideration with additional conditions such as risk-sharing agreements. Given the extended efforts over the past 2-4 years to secure reimbursement. The outcome of 'Vyndamax’s' approval will serve as a significant precedent.

Additionally, Bridge Biotherapeutics and Bayer are co-developing 'Acoramidis', which has already gained FDA approval and may eventually enter Korea. AstraZeneca and Ionis Pharmaceuticals’ 'Eplontersen' is also anticipated to be introduced in the future.

Gaucher Disease

In Korea, Gaucher Disease is primarily managed with enzyme replacement therapies (ERT) such as Sanofi's 'imiglucerase' ('Cerezyme') and Takeda's 'velaglucerase alfa' ('Vpriv'). These treatments are effective for systemic symptoms but do not address neurological involvement due to their inability to cross the BBB. 'Eliglustat' ('Cerdelga'), an oral substrate reduction therapy developed by Sanofi, is available for patients with type 1 Gaucher Disease who are CYP2D6 extensive metabolizers. Additionally, ISU Abxis's 'Abcertin' is another treatment option available in the market.

Gaucher Disease has also shown positive outcomes with chaperone therapy when combined with ambroxol, especially in cases with neurological symptoms. There is growing interest in exploring the relationship between Gaucher Disease and Parkinson's disease, leading to further research in this area. In Asian populations, including Korea, over 50% of patients with neurological symptoms have type 3 Gaucher Disease. Improving treatment for this type could present a significant opportunity. Research is focused on developing small molecule therapies capable of penetrating the BBB, offering hope for patients with neuronopathic Gaucher Disease.

Summary

These conditions represent the most significant unmet needs in the Korean rare disease market, requiring additional treatment options and presenting a strategically attractive market for growth. The Korean market for rare diseases is poised for significant advancements, especially in the treatment of HAE, hATTR, and Gaucher Disease.

These conditions, marked by substantial unmet needs, are benefiting from innovative approaches like preventive therapies, indication expansion, and the development of small molecules capable of crossing the BBB. As these therapies continue to evolve, they promise to transform the management of rare diseases, ultimately improving patient outcomes and quality of life. The potential for these markets is promising, and the introduction of paradigm-shifting treatments is urgently needed to meet the growing demand.