At the beginning of March 2021, gene therapy company AVROBIO, Inc. shared that its investigational gene therapy, AVR-RD-04, was given Orphan Drug designation by the European Commission (EC). This treatment is designed to treat patients with cystinosis.

AVR-RD-04

According to the EC, this special status is granted to products:

intended for the diagnosis, prevention or treatment of life-threatening or very serious conditions that affect no more than 5 in 10,000 people in the European Union.

AVR-RD-04 has also received Orphan Drug designation within the United States. In this case, it is granted to products which serve patients with rare diseases, or those which affect under 200,000 Americans.

So how does AVR-RD-04 work? This is an ex vivo treatment. The American Society of Gene + Cell Therapy states that ex vivo means that:

the targeted cells are removed from the patient and gene therapy is administered to the cells in vitro before they are returned to the patient’s body.

In this case, patients’ hematopoietic stem cells are removed from the body. Next, the stem cells are genetically modified. Once modified, the cells express cystinosin, which is deficient in patients with cystinosis. They are then injected back into the body in what AVROBIO hopes will be a singular gene therapy treatment. Currently, researchers are exploring the safety, efficacy, and tolerability of AVR-RD-04 in a Phase 1/2 clinical trial.

Cystinosis

CTNS gene mutations cause cystinosis, a rare inherited disorder characterized by the accumulation and crystallization of cystine in bodily cells. Cystine is a type of amino acid. Normally, cystine occurs naturally in the body and is transported throughout the body. But patients with cystinosis have a cystinosin deficiency, which makes it difficult or impossible to transport cystine. Thus, cystine becomes trapped in lysosomes. Without treatment, patients may experience organ damage or kidney failure. Additionally, cystinosis can be fatal.

Generally, there are three main forms of cystinosis: nephropathic, intermediate, and non-nephropathic (ocular). In the first and most severe form, patients generally show symptoms around late infancy. These symptoms include:

• Excessive thirst
• Rickets (the softening and weakening of bones)
• Cystine crystallization in the eyes
• Nutrient loss through urine

In the second form, many symptoms are the same. However, intermediate cystinosis usually manifests later than infancy. Finally, non-nephropathic cystinosis has corneal crystals but tends to lack the more severe symptoms of other forms. If the eyes are affected, it can cause sensitivity to light and, in severe cases, blindness.

A large majority of patients will eventually require a kidney transplant and other treatment options are often burdensome, inefficient, and invasive. For this reason, new treatment options are needed. Outside of affecting the kidney, cystinosis may also affect the:

• Liver
• Central nervous system (CNS)
• Thyroid
• Muscles
• White blood cells

Learn more about cystinosis.