Promising Rare Diseases in the Korean Market 1: From Established Treatments to Next-Generation Therapies

I would like to introduce “Promising Areas in the Korean Rare Disease Market.”

Among the conditions with established markets and available treatments, such as Duchenne Muscular Dystrophy (DMD), Spinal Muscular Atrophy (SMA), Hemophilia, and Lysosomal Storage Disorders (LSDs) like Fabry disease and Mucopolysaccharidosis (MPS), there are exciting developments underway.

With the advancement of groundbreaking therapies, including gene treatments, these areas are expected to see significant progress in the near future.

Promising Rare Diseases in the Korean Market 1: From Established Treatments to Next-Generation Therapies

Over the past few decades, the Korean market for rare diseases has grown steadily. Treatments for major conditions like Duchenne Muscular Dystrophy (DMD), Spinal Muscular Atrophy (SMA), Hemophilia, and Lysosomal Storage Disorders (LSDs) have already set the stage. However, the rise of gene therapies and new treatment methods is quickly changing how these diseases are treated. This article looks at the expected developments in major rare diseases and therapies in Korea.

Neuromuscular Diseases: Pioneering New Frontiers in Therapy

DMD and SMA are some of the most researched neuromuscular diseases, with ongoing work on both existing treatments and new gene and RNA-based therapies.

Duchenne Muscular Dystrophy (DMD): This genetic disorder, linked to the X chromosome, leads to muscle weakening because of a lack of dystrophin. Traditional treatments include steroids and exon-skipping drugs. In Korea, options like Viltolarsen, Golodirsen, and Casimersen, which are approved in the US and Japan, are not available. Sarepta Therapeutics' Elevidys, a gene therapy that boosts dystrophin production, is approved in the US and being considered for Korea. New therapies like peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are in global trials, with active RNA-based research happening in Korea.

Spinal Muscular Atrophy (SMA): This rare disease causes motor neurons to break down, making timely treatment very important. In Korea, Biogen's Spinraza is given through spinal injection, while Roche's Evrysdi is taken orally. Novartis' Zolgensma, a one-time gene therapy given intravenously, restores SMN1 gene function but is expensive and not easily accessible. While DMD treatments are still limited, the SMA field is leading in adopting gene therapies, with more advancements like Elevidys expected. However, cost-effectiveness remains a key issue, as seen with Zolgensma.

Hemophilia: Factor Replacement to Gene Therapy

Hemophilia treatment has traditionally relied on replacing Factor VIII/IX, but now extended half-life and gene therapies are offering more options.

Treatments with extended half-lives like Eloctate and Alprolix are covered by insurance in Korea, reducing how often they need to be given and easing the burden on patients. Roche's Hemlibra, in partnership with JW Pharmaceutical, is given as a subcutaneous injection, making it more convenient and receiving positive feedback. Expanding the range of conditions covered by insurance is expected to strengthen its market position.

While many global companies have tried to develop AAV-based gene therapies for hemophilia, success has been limited. Recently, BioMarin's Roctavian was approved in Europe and the US, and CSL Behring's Hemgenix is gaining attention for treating hemophilia B. Although these are not yet available in Korea, efforts are being made to speed up their introduction and insurance coverage.

Lysosomal Storage Disorders (LSDs): ERT to Advanced Solutions

Lysosomal storage disorders (LSDs) are rare diseases caused by genetic enzyme deficiencies, leading to the buildup of certain substances. Enzyme replacement therapy (ERT) is standard, but new developments in gene and small molecule therapies are promising.

• Fabry Disease: This condition is due to a lack of the α-galactosidase A enzyme, causing kidney and heart problems. In Korea, Fabrazyme, Replagal, and the biosimilar Fabagal are used and covered by insurance. Amicus' Galafold, an oral treatment for specific genetic mutations, is available through Handok. Chiesi's Elfabrio, a next-generation pegylated ERT, is being prepared for launch with KwangDong Pharmaceutical. Additionally, leading domestic pharmaceutical companies, Hanmi Pharmaceutical and Green Cross (GC Pharma), are collaborating on a Phase 2 clinical trial for a subcutaneous (SC) administration of a Fabry disease treatment, raising expectations for further improvements in the future.

  
  

• Mucopolysaccharidosis (MPS): This group of disorders is divided into various types, each with different treatments. MPS I is treated with Aldurazyme, available in Korea. MPS II (Hunter syndrome) is treated with Elaprase and its Biosimilar, Hunterase developed by GC Pharma. MPS III (Sanfilippo syndrome) has limited options, with no ERT available, but companies like Abeona Therapeutics and Lysogene are developing gene therapies. Participation in global trials is needed to expand options in Korea. MPS IV (Morquio syndrome) is treated with BioMarin's Vimizim, and MPS VI (Maroteaux-Lamy syndrome) with Naglazyme, both of which are provided in Korea by Samoh Pharma. Ultragenyx's Mepsevii is anticipated for MPS VII (Sly syndrome).

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In MPS, key areas for improvement include developing small molecules that can cross the blood-brain barrier and intrathecal administration to address neurological symptoms. Innovations like IT ERT and JCR's J-Brain Cargo technology applied to JR-141 are promising. Future developments in gene therapies for other MPS types, such as MPS III, are also anticipated.

Conclusion

Among the rare diseases introduced, these conditions already have a well-established patient base receiving diagnosis and treatment in Korea. As a result, this area presents the highest potential for the introduction of new therapies.

The shift to next-generation therapies in established rare disease markets is poised to address unmet needs, such as alleviating neurological symptoms, exploring innovative treatment methods, and enhancing the delivery of care. These markets, already well-defined by specific diseases, present attractive opportunities for new therapies to enter and thrive. Despite the challenges in developing and commercializing gene therapies, particularly those based on AAV, significant progress is being made. While real-world effectiveness and cost remain important considerations, the outlook is promising.

Ultimately, as gene therapies continue to demonstrate their effectiveness and as cost challenges are addressed, they are expected to become more accessible. This will lead to more personalized and improved care for patients with rare diseases. This progress not only offers hope for better outcomes but also heralds the beginning of a new era of significant advancements in treatment.