Fast track designation is granted by the FDA. If a drug developer receives this designation, they begin a process to develop and expedite review for drugs or biologics which treat rare or serious conditions, or provide a therapy where none exists or that can show promise over current treatment options. Recently, biopharmaceutical company Denali Therapeutics Inc. (“Denali”) shared that its investigational drug candidate DNL310 (ETV:IDS) for Hunter syndrome (MPS II) received Fast Track designation.
One of Denali’s main company goals is to develop therapies which are able to cross the blood-brain barrier, potentially introducing better treatment for neurodegenerative diseases or conditions. For patients with Hunter syndrome, this is a difficulty with current treatments. While enzyme replacement therapy does benefit patients, it is unable to cross the blood-brain barrier and significantly treat underlying issues. Currently, Denali believes that DNL310 has the ability to overcome this issue.
So what is DNL310? DNL310 is a fusion protein. It is composed of IDS, which is then fused to Denali’s proprietary Enzyme Transport Vehicle (ETV). After being intravenously administered, DNL310 crosses the blood-brain barrier using receptor-mediated transcytosis. As a result, it is able to treat peripheral and central nervous system (CNS) manifestations of Hunter syndrome. The therapy is being explored in a Phase 1/2 clinical trial, which is still enrolling.
Denali’s transport vehicle (TV) platform helps protect the brain’s microenvironment while still delivering an adequate amount of therapies to the brain. It is able to cross the blood-brain barrier using engineered Fc fragments and transferrin receptors.
Hunter Syndrome (MPS II)
Also known as mucopolysaccharidosis type II (MPS), Hunter syndrome is a rare, progressive genetic disorder. A defective gene, inherited (usually) by a male fetus, causes Hunter syndrome. The condition is incredibly rare in females. Normally, this specific gene helps to produce the enzyme iduronate-2-sulfatase (IDS), which breaks down complex sugar molecules. However, the mutation prevents that from occurring. Thus, the sugar molecules begin to collect in the cells, causing health difficulties. MPS II may be mild or severe. Unfortunately, those with the severe form do not have a very good outlook, while those with the milder form may live longer, especially due to improved treatments.
Signs and symptoms typically appear between 2-4 years old. These include:
- Full lips and an enlarged tongue
- Large rounded cheeks and a broad nose
- Hydrocephalus (fluid build-up in the brain)
- Macrocephaly (an enlarged head)
- A deep, hoarse voice
- Spleen and liver enlargement
- Inguinal hernia
- Abdominal distension
- Chronic diarrhea
- Stunted growth
- Developmental delays
- Joint stiffness
While Hunter syndrome does not have a cure, treatments like enzyme replacement therapies may help with disease management.