Companies develop new drugs for Fabry disease

Companies seek various candidates to overcome the rare Fabry disease

Phase I/II IND approved for Hanmi, GC Biopharma… will start multinational clinical trials

Developed as a subcutaneous injection formulation...a single-shot gene therapy is also being researched

Domestic and foreign pharmaceutical companies are speeding up the development of new drugs for the rare Fabry disease.

 

They aim to develop treatments that improve not only efficacy and safety but also administration methods compared to existing treatments.

 

According to industry sources on the 15th, the Ministry of Food and Drug Safety recently approved the Phase I/II clinical trial plan (IND) for LA-GLA, a new drug candidate for Fabry disease being jointly developed by GC Biopharma and Hanmi Pharmaceutical.

 

The two companies entered multinational clinical trials in August last year after receiving approval in the U.S.

 

and Korea.

 

Fabry disease is a rare disease that is inherited as a sex chromosome and is a type of Lysosomal Storage Disease (LSD).

 

It is caused by a deficiency of the enzyme ‘alpha-galactosidase A,’ which breaks down glycolipids in lysosomes, an organelle in cells that remove unnecessary substances.

 

The continuous accumulation of unprocessed glycolipids in the body leads to cytotoxic and inflammatory reactions, and progressive damage to various organs, eventually leading to death.

 

LSD is caused by a genetic deficiency of certain enzymes, resulting in metabolic abnormalities.

 

Lysosomes, which are organelles within cells, contain enzymes that break down substances that the body no longer needs.

 

When these enzymes are impaired or not produced, substances that should be broken down gradually accumulate in the cell.

 

Fabry disease, mucopolysaccharidosis, Pompe disease, and Gaucher disease, are typical examples of LSD.

 

In 2020, Hanmi Pharmaceutical and GC Pharma signed an agreement to jointly develop next-generation innovative drugs for the treatment of LSD and are conducting joint research with the goal of developing global innovative drugs in the field of rare diseases.

 

LA-GLA, a new drug candidate for Fabry disease being developed by the two companies, is a next-generation long-acting enzyme replacement therapy that improves the limitations of existing treatments.

 

GC Biopharma and Hanmi Pharmaceutical plan to develop LA-GLA into a subcutaneous injection formulation that can be administered once a month.

 

Most Fabry disease patients are treated with enzyme replacement therapy (ERT), an intravenous injection of enzymes developed by gene recombination technology.

 

Sanofi

Currently, Sanofi's Fabrazyme, Takeda's Replagal, Handok's newly introduced drug Galafold, and ISU Abxis’ Fabrazyme biosimilar Fabagal are being currently used in Korea.

 

All but Galafold are intravenous ERT formulations.

 

Galafold is an oral formulation that is more convenient to administer, but it is not available until after a year of ERT-based therapy.

 

ERT-based therapies are known to have limitations, including the inconvenience of long intravenous infusions every 2 weeks in the hospital and the lack of efficacy in controlling advanced kidney disease.

 

In preclinical studies, LA-GLA has been shown to improve kidney function and fibrosis compared to existing therapies, and in an animal model with Fabry disease, LA-GLA significantly improved peripheral sensory function and histologic lesions of the nerve cells that control it and was effective in improving the increase in blood vessel wall thickness caused by glycolipid accumulation.

 

LA-GLA was designated as an orphan drug (ODD) by the U.S.

 

Food and Drug Administration (FDA) in May based on its efficacy in improving kidney function, vascular disease, and peripheral nerve disorders compared to existing therapies in the clinical stage.

 

Gene therapy also in development The global pharma and biotech industry also has the potential for new drugs for Fabry disease through single-dose gene therapy.

 

Last month, the FDA granted orphan drug designation to Exegenesis Bio’s Fabry disease drug candidate 'EXG110'.

 

EXG110 is a single-dose gene therapy candidate designed to clone the GLA gene and deliver it to liver and heart cells.

 

The drug candidate utilizes an adeno-associated virus (AAV) to deliver the therapeutic gene.

 

AAV is a virus that does not cause disease in humans and is characterized by its ensured safety.

 

Exogenesis is currently conducting clinical trials in Fabry disease patients in China.

 

The first patient has now been dosed with EXG110.

 

The company plans to seek approval in the U.S.

 

for a multinational trial.

 

In September of last year, Unicure's Fabry disease drug candidate AMT-191 was granted orphan drug designation in the United States.

 

AMT-191 is a gene therapy designed to target the liver to produce the GLA protein.

 

Unicure is conducting a Phase I/II clinical trial of AMT-191 in the United States.

 

Unicure plans to administer AMT-191 to 6 patients with Fabry disease to measure the expression of the lysosomal enzyme aGLA-A and evaluate the safety, tolerability, and efficacy of the candidate.