‘Even a 0.2 vision is a miracle to some’

Professor Suk Ho Byeon, Department of Ophthalmology, Sinchon Severance Hospital

“A treatment option for IRD mutation-associated IRD born... only 6 patients exist in Korea”

“Need criteria for drug reimbursement evaluations that consider the specificity of the disease and its patients"

Professor Suk Ho Byeon

The reason for the slow development of new drugs in a specific disease can usually be attributed to one of the following two reasons.

 

Low disease awareness or difficulty in developing the drug itself.

 

The one-shot gene therapy Novatis’s ‘Luxturna (voretigene neparvovec)’ is a drug that overcame both barriers.

 

Luxturna, which is a treatment for IRD (Inherited Retinal Dystrophy) caused by the mutation in both copies of the RPE65 gene, is the first treatment option developed for the difficult rare genetic condition.

 

IRD is a rare intractable disease caused by a mutation in the gene responsible for the structure and function of retinal visual cells.

 

It includes over 20 types of ophthalmologic conditions, and around 270 causal genes are known to be implicated in IRD.

 

RPE65-IRD, caused by the mutation in both copies of the RPE65 gene, causes abnormalities in the visual cycle of the retina that converts visual information into a neural signal and delivers it to the brain.

 

The mutation in the RPE65 gene reduces the RPE65 protein essential to the visual cycle and destroys the retinal cell, gradually narrowing the field of vision to eventually result in loss of vision.

 

With only 6 patients found with IRD in Korea, patients with the condition reach legal blindness in their adolescence, at about 16 to 18 years of age, then progress to complete blindness.

 

Due to the lack of a fundamental cure, only conservative treatment that could temporarily delay symptoms was available until now.

 

WIth its release, Luxturna became the first drug introduced into the field that could prevent blindness.

 

Dailypharm met with Professor Suk Ho Byeon, Department of Ophthalmology at Sinchon Severance Hospital to hear about the significance of RPE65-IRD and Luxturna.

 

Professor Byeon had recently coauthored a consensus paper on RPE65-IRD published in the Korean Journal of Ophthalmology, an English journal published by the Korean Ophthalmological Society.

 

-The consensus paper you released recently seems to have covered the whole content on RPE65 mutation-associated IRD starting from its concept.

 

It felt more like a clinical practice guideline.

 

Does the fact that this paper was published signify the lack of content on the diagnosis and management of RPE65-IRD in Korea? It can be said so.

 

Due to the characteristics of the disease, treatment is rare in any form of IRD.

 

Not many doctors have experience using drugs to treat the disease.

 

So we tried to relay the existence of such a disease and the need to look for the disease.

 

With the first drug released fRPE65-IRD, hope is rising among all IRD patients including those with genetic mutations other than the RPE65 mutation.

 

However, since there was little information arranged on the disease itself as well as its diagnosis and treatment, we decided to bring together experts who had experienced or were familiar with the disease in Korea to arrange the information on the disease.

 

The consensus paper includes information on what RPE65-IRD is, what kind of patients are considered to have IRD, its global epidemiology and epidemiology in Korea, to which extent genetic mutations are reported, and how and whom should receive gene tests for the disease.

 

-As you’ve mentioned, the consensus paper includes content on finding the subjects that should receive genetic testing.

 

Which parts should the doctor check during gene testing? One of the most prominent characteristics in these patients is that they had poor eyesight from an early age.

 

This may be difficult to notice during infancy, but over time, the patient’s eyesight decreases significantly compared to normal people and is accompanied by night blindness.

 

However, with so many areas bright at night, night blindness is sometimes discovered late these days.

 

Patients with severe symptoms also experience eye tremors.

 

However the features of the disease can vary even among patients affected with the same genetic mutation.

 

Some patients show fewer symptoms and some do not have night blindness.

 

Therefore, the disease is difficult to identify based solely on symptoms.

 

Therefore, in pediatric patients, I think it is better to proceed and conduct a genetic test even if at the smallest suspicion.

 

-So Luxturna was released in the field that had no available drugs.

 

The drug received attention as the first gene therapy for ophthalmic diseases.

 

What is your opinion on the value of the drug? That would be difficult for general ophthalmologists to judge.

 

I can better explain its significance because I have experience treating patients with Luxturna.

 

Patients with poor eyesight ever since childhood rarely visit the hospital, so doctors often do not know how these patients are faring.

 

In that sense, it is difficult to estimate how much a patient's life would have improved with improved eyesight.

 

Ophthalmologists measure both visual acuity and visual fields.

 

This index of visual acuity and field of view measures how far off the patients’ eyesight is from those of normal people.

 

Patients who were treated with Luxturna showed much improvement in the visual field and visual acuity.

 

The improved visual acuity was about 0.2.

 

For non-patients, visual acuity of 0.2 may feel like a poor condition, but for those that had almost no vision, even a 0.2 vision can be of great benefit.

 

I was very surprised to see a patient I treated working part-time at a coffee shop.

 

A patient who could go blind escaped the danger with Luxturna.

 

In this sense, the effect of such treatment should not be judged based on standards set for normal eyes.

 

- Luxturna received the non-reimbursement decision last month from the National Health Insurance Review and Assessment Service’s Drug Reimbursement Evaluation Committee.

 

The committee pointed to how the condition is not life-threatening and is a high-priced drug as a barrier to reimbursement.

 

There also seems to be a difference between the government and pharmaceutical companies regarding reimbursement standards. Reimbursement is a complex issue that requires broad and serious considerations.

 

Since Luxturna is a gene replacement therapy, I know there have been disagreements on the remaining target cell and the criteria for recognizing its effect.

 

As a doctor, I can definitely say that there can be no crystal-clear standard for evaluating living cells.

 

Some cases can only be determined after treatment.

 

Since it is such a rare condition, it is difficult to even estimate how many cases there will be.