Hanmi Pharm and GC Biopharma have gotten on track to develop a new treatment for Fabry disease with longer-lasting effects than existing treatments.

Hanmi Pharm and GC Biopharma presented two posters on the results of nonclinical studies of LA-GLA (code name HM15421/GC1134A), a candidate for Fabry disease, at the WORLD Symposium 2024 in San Diego, Calif., held from Jan. 4 to 9 (local time).

The two companies signed a collaboration agreement in 2020 to jointly develop innovative drugs for lysosomal storage diseases (LSD). With the release of the nonclinical study results, nearly four years after the agreement, the companies have revealed their specific goal of developing a once-monthly subcutaneous Fabry disease treatment.

Fabry disease is a rare, inherited metabolic disorder caused by a deficiency of the enzyme alpha-galactosidase A (α-gal A), which breaks down glycolipids. This causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the body, disrupting the function of cells and tissues and eventually damaging organs.

One of the main treatment strategies for Fabry disease is enzyme replacement therapy (ERT), which involves injecting artificially recombinant enzymes into the body to replenish deficient enzymes and includes Sanofi's Fabrazyme (agalsidase beta) and Takeda's Replagal (agalsidase alpha). Both are intravenous injections.

The two Korean companies emphasized that existing enzyme replacement therapy treatments require patients to go to the hospital every two weeks and receive intravenous injections for several hours, adding that LA-GLA has been confirmed to be superior in improving kidney function, vascular disease, and peripheral neuropathy compared to existing agalsidase beta-based treatments.

These companies said they would overcome the limitations of existing drugs by targeting Fabrazyme, the leading drug for Fabry disease. Fabrazyme requires patients to visit a clinic every two weeks to receive an intravenous infusion of the drug over four to five hours.

The current dosing cycle is burdensome for patients, which the medical community agrees with. In particular, because it is a rare disease treatment, patients with rare diseases outside the Seoul metro region must travel long distances to receive the treatment at a regional medical center.

However, competition among Fabry disease treatments remains fierce.

Replagal, launched later than Fabrazyme in Korea, emphasizes that it is derived from a human cell line rather than an animal cell line, claiming to have a simple pre-treatment and a short dosing time of 40 minutes due to the low immunogenicity of patients.

On the other hand, long-standing clinical studies have demonstrated Fabrazyme's long-term protective effect and safety profile. Also, higher doses of Fabrazyme compared to Replagal have effectively reduced the accumulation of glycolipids that cause Fabry disease symptoms.

Although not an enzyme replacement therapy, oral Fabry disease treatments have also been developed to improve the convenience of administration. Handok is introducing an oral Fabry disease treatment called Galafold (migalastat), which can be used for patients with compliant variants and is prescribed for up to 60 days in Korea.

A Korean company also has succeeded in developing a Fabry disease biosimilar. Isu Absix, an affiliate of the Isu Group, has commercialized Fabagal, a Fabrazyme biosimilar, supplying the product domestically and internationally. Last year, the company said it achieved 10.2 billion won (7.65 million) in domestic sales due to increased prescriptions.

Despite fierce competition, the high market growth rate despite existing prescription competition is expected to drive the two Korean latecomers to develop a new drug. According to global market research firm Evaluate Pharma, the Fabry disease treatment market is expected to grow at an annualized rate of 9.6 percent from $1.9 billion (about 2.53 trillion won) in 2023 to $3 billion in 2028.

Hanmi Pharm and GC Biopharma plan to apply for orphan drug designation (ODD) and enter phase 1 clinical trial within the year. The industry is also interested in which company will lead the trials. However, both remain tight-lipped. Hanmi Pharm said it is difficult to disclose as it is contract-related.

"The R&R (roles and responsibilities) of the two companies will be derived later," a GC Biopharma official said.