Oral Therapy TRE-515 Wins Orphan Drug Status for Optic Neuritis in US

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Trethera Corporation’s experimental oral therapy TRE-515 for demyelinating optic neuritis, an eye condition that may progress to multiple sclerosis (MS) or occur during the disease course.

The first-in-class therapy is expected to lessen the inflammation and abnormal immune responses that damage myelin, the protective sheath around nerve fibers that is lost in both demyelinating optic neuritis and MS. Demyelination is the process of myelin loss.

“For some patients, ON [optic neuritis] can be self-resolving, but for others ON can lead to lifelong disability,” Larry Steinman, MD, Trethera’s scientific advisory board member, said in a company press release.

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“In all ON cases, the threat of future conversion to MS remains,” Steinman said, adding that “any drug that could improve these outcomes for patients would be game changing.”

“TRE-515 could potentially significantly benefit ON patients beyond the available therapeutic options, especially those taking long-term steroids,” added Steinman, a professor of neurology and neurological sciences, pediatrics, and genetics at Stanford University.

Orphan drug designation

Orphan drug status is given to treatment candidates that may significantly benefit people with life-threatening or chronically debilitating diseases that affect fewer than 200,000 people in the U.S.

This designation is meant to accelerate TRE-515’s clinical development and review by providing regulatory support and financial benefits, as well as a seven-year marketing exclusivity period upon regulatory approval, if granted.

“The FDA designation for the treatment of ON complements our existing exclusive [orphan drug designation] for acute disseminated encephalomyelitis (ADEM) and provides key external validation that continues to showcase the strength of our scientific data,” said Ken Schultz, MD, Trethera’s chairman and CEO.

“TRE-515 is developing an impressive resume for potential treatments of demyelinating autoimmune diseases,” Schultz added.

Similar to MS, ADEM is an autoimmune disease in which the immune system abnormally attacks myelin in the brain and spinal cord. ADEM, a rare condition, typically consists of a single demyelinating event, while MS is characterized by multiple events.

Optic neuritis, which affects more than 100,000 people annually in the U.S., is characterized by inflammatory damage to the optic nerves that send visual signals from the eyeballs to the brain. It usually occurs in one eye at a time and can result in several vision problems, with one in 10 patients never fully recovering their eyesight.

About 70% of MS patients experience optic neuritis at some point in their lives, being the first symptom in 20% of them. However, not everyone with optic neuritis will develop MS.

Steroids, a type of anti-inflammatory and immunosuppressive treatment, are associated with faster optic neuritis recovery and reduced conversion to MS in the first two years. But they have no effect on long-term visual outcomes or MS conversion as measured after five years.

TRE-515 is a first-in-class oral therapy that works by potently blocking deoxycytidine kinase (dCK), an enzyme involved in T-cell and B-cell development, two types of immune cells implicated in MS and other autoimmune demyelinated diseases.

The enzyme plays a key role in a metabolic pathway that recycles products of DNA degradation.

“Inflammation damaging the protective myelin coating around the optic nerve causes ON, leading to pain and vision loss. Targeting dCK with TRE-515 could limit this inflammation,” said Peter Clark, PhD, member of the Trethera scientific advisory board.

Notably, dCK is also implicated in cancer cell growth, and Trethera is also exploring TRE-515 as a potential cancer treatment.