In a recent press release, clinical-stage gene therapy company Rocket Pharmaceuticals, Inc. (“Rocket”) shared that its investigational gene therapy candidate, RP-L201, received Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). The gene therapy is designed for patients with Leukocyte Adhesion Deficiency type 1 (LAD-1).

Leukocyte Adhesion Deficiency Type 1 (LAD-1)

According to MedLine Plus:

Leukocyte adhesion deficiency type 1 is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as viruses, bacteria, and fungi.

ITGB2 gene mutations cause leukocyte adhesion deficiency type 1 (LAD-1). Normally, this gene encodes for CD18, a protein that helps direct leukocytes (a type of white blood cell) to wounds or infections. Without enough CD18, patients with LAD-1 are immediately subject to a host of bacterial and fungal infections. Typically, these appear soon following birth. The infections may be severe and life-threatening. Additionally, many infections faced by those with LAD-1 are often treatment averse. While patients can, in some cases, be treated with bone marrow transplants, these are not always successful. Because of this, the mortality rate associated with LAD-1 is high, with most not surviving past age 2.

Symptoms of LAD-1 are varied but may include:

• Delayed detachment of umbilical cord stump
• Septicemia (blood poisoning)
• Umbilical cord stump inflammation (omphalitis)
• Gingivitis and periodontitis
• Tooth loss
• Slow-healing wounds
• Pneumonia
• Ulcers in the gums or on the skin
• Frequent bacterial and fungal infections without pus formation

RP-L201

So what is RP-L201? Currently, Rocket is developing this gene therapy solution to address unmet patient needs in regards to LAD-1. Initially, the therapy was in-licensed. RP-L201 is created using genetically modified autologous hematopoietic stem cells. According to the Mayo Clinic:

An autologous stem cell transplant uses healthy blood stem cells from your own body to replace your diseased or damaged bone marrow.

In this case, the stem cells are modified using a lentivirus viral vector (LVV). Once administered back into the body, RP-L201 delivers functional ITGB2, assisting with the promotion of CD18. Currently, the treatment has received Orphan Drug, Rare Pediatric, Fast Track, and Regenerative Medicine Advanced Therapy designations within the United States. In the European Union, the treatment has Orphan Drug, Advanced Therapy Medicinal Product, and PRIME designations.

The recent PRIME designation was based on safety and efficacy results from a Phase 1/2 clinical trial. Ultimately, a therapy cannot receive this designation without having data that supports its potential ability to fulfill some unmet patient need. The EMA describes PRIME as:

a scheme launched by the European Medicines Agency (EMA) to enhance support for the development of medicines that target an unmet medical need. This voluntary scheme is based on enhanced interaction and early dialogue with developers of promising medicines, to optimise development plans and speed up evaluation so these medicines can reach patients earlier.