‘Biobetter Nexviazyme is a better treatment option'

Professor Hyunjoo Lee, Department of Pediatrics, Gangnam Severance Hospital

Provides less damage to muscle cells and improves immunogenicity

Reimbursement needs to be extended to diagnosis, such as screening tests, etc

Professor Hyunjoo Lee

There are times when a single treatment has a significant impact on the overall management of the disease.

 

This is especially true for rare and incurable diseases.

 

In the field of metabolic diseases, a paradigm shift occurred when researchers found that certain rare patients lacked a single enzyme, which led to the development of therapies to introduce a substitute into the body to fulfill the enzyme’s role.

 

As a result, patients suffering from these conditions, which are referred to as ‘LSDs (Lysosomal Storage Diseases),’ include Hunter syndrome, Gaucher disease, Fabry disease, and Pompe disease, are currently being treated with enzyme replacement therapy (ERT).

 

Among these diseases, recent advances have been made in the treatment landscape of Pompe disease.

 

About a decade after the ERT drug Myozyme (alglucosidase alfa) was introduced, the biobetter Nexviazyme (avalglucosidase alfa-ngpt) has been granted reimbursement coverage in Korea.

 

Nexviazyme, which was added to the reimbursement list in September last year, became the first drug to receive pricing benefits as a biobetter in Korea.

 

Dailypharm met with Hyunjoo Lee, Professor of Pediatrics at Gangnam Severance Hospital, to learn more about the significance of Nexviazyme’s arrival in Korea.

 

-Nexviazyme can now be prescribed with reimbursement in Korea.

 

What is the benefit of this new treatment option? Pompe disease is a progressive, genetic neuromuscular disease.

 

Despite the many advances in the treatment landscape, there still remained an unmet need as patients were unable to achieve 100% improvement with existing treatments.

 

Nexviazyme was developed to address this unmet need.

 

Nexviazyme is a biobetter drug that was approved for its improved formulation and advancements over the existing Myozyme.

 

It increases intracellular drug uptake by expressing approximately 15 times more mannose 6-phosphate (M6P) on the surface of the therapeutic enzyme than existing therapies.

 

As a result, it can reduce muscle cell damage through effective glycogenolysis by improving glucosidase activity, and it is also beneficial in terms of safety due to improved immunogenicity.

 

-Could you elaborate on the unmet needs that had existed in Korea? Pompe disease is divided into 2 types: infantile-onset Pompe Disease (IOPD), and late-onset Pompe Disease (LOPD), which is characterized by irreversible muscle damage.

 

Myozyme use in patients with infantile-onset Pompe disease has been associated with rapid improvement in heart-related symptoms, such as enlargement of the heart, but there remained room for improvement in muscle-related symptoms, which did not improve 100% and progressed over time.

 

Patients with Pompe disease experience ongoing issues, such as difficulty walking due to arm and leg muscle damage and breathing difficulties due to respiratory muscle damage, but they had limited options as there was only one treatment available for their use.

 

- I understand that forced vital capacity (FVC) and the ability to walk were key endpoints in the Nexviazyme trial. That is correct.

 

In addition to cardiac symptoms, improvements in respiratory and skeletal muscles are important in Pompe disease, to the extent that researchers seek to understand which muscles are most affected.

 

This is most often determined by a six-minute walk test or a forced vital capacity test, but since the walk test cannot be conducted on pediatric patients, symptom improvement in these patients is determined by respiratory and infectious disease susceptibility, and muscle strength for daily activities.

 

The FDA approval in late-onset Pompe disease was granted first for Nexviazyme because of the drug’s effect in improving skeletal muscle, respiratory failure, and muscle-related symptoms.

 

- Are there any risks associated with long-term treatment with Nexviazyme? Because it is an injectable, an infusion-related reaction may occur.

 

Also, regular hospital visits are needed for the injections, which can be challenging.

 

Younger children may have difficulty with vascularization, but there are no other risks.

 

- I remember a few years ago, there was a lot of talk on the need to improve the diagnostic system for genetic diseases such as Pompe disease.

 

What is the current diagnostic landscape like for Pompe disease in Korea?

 

Early diagnosis is important in infantile-onset Pompe disease because of its rapid symptom progression, which can to severe cardiorespiratory disorders and death within a year if the patient does not start treatment immediately.

 

In Korea, diagnostic testing itself is not difficult due to good medical access, and since January this year, lysosomal storage diseases have been included in the neonatal screening test, which means that many patients will be diagnosed more quickly.

 

This is expected to increase the diagnosis rate of lysosomal storage diseases and enable better collection of accurate data about the disease, including the prevalence of Pompe disease patients in Korea.

 

- Lastly, what area do you think needs improvement in the Pompe disease treatment environment? Despite much support from the government, relevant organizations, and pharmaceutical companies, there still are some neglected areas that require attention.

 

For example, in adults, we can evaluate the patient's improvement through FVC and 6-minute walk tests, etc.

 

but it is difficult to do these tests on children.

 

Urine tests are a good option, but these tests are often performed overseas, making it difficult to find out the results immediately.

 

I hope that national or rare disease organizations will recognize this need and create a system to enable efficient testing in Korea.

 

False positives can occur in newborn babies that are born too small or prematurely, depending on their condition.

 

In such cases, I believe the additional tests that are performed at the discretion of the doctor on these patients should also be covered.

 

Also, screening newborns after 28 days of age or those with late-onset Pompe disease is not reimbursed in Korea, and I would like the initial screening process for these patients to be covered so that those with late-onset Pompe disease can be more proactively diagnosed.