There are limited therapeutic interventions for those living with Niemann-Pick disease type C (NPC), a rare and progressive genetic disorder. Unfortunately, many people with NPC experience severe and life-threatening complications by the second or third decade of life. A lack of treatment options represents an immense unmet need within this community. Currently, Azafaros B.V., a biotechnology company aiming to develop therapies for rare metabolic diseases, is working to fill this unmet need.

News shared in Markets Insider states that Azafaros B.V. recently completed the 12-week Phase 2 RAINBOW clinical trial. During the trial, researchers evaluated Azafaros B.V.’s drug candidate nizubaglustat for 13 individuals (ages 12+) with NPC. Nizubaglustat is an orally available azasugar that inhibits both ceramide glucosyltransferase and non-lysosomal glucosylceramidase. It is able to cross the blood-brain barrier for more targeted treatment. This therapy has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the US FDA, as well as other accolades from the European Medicines Agency. Outside of NPC, Azafaros B.V. is exploring nizubaglustat as a therapeutic option for Tay-Sachs disease and Sandhoff disease.

Within the Phase 2 RAINBOW study, researchers sought out to understand:

• How safe the drug was for use in this population
• The pharmacodynamics and pharmacokinetics of two separate nizubaglustat doses
• What dose should be used for further studies

All participants are now entering the trial’s extension phase. Data should be available later this year.

An Overview of Niemann-Pick Disease Type C (NPC)

Niemann-Pick disease type C is a rare, inherited metabolic disorder caused by NPC1 or NPC2 gene mutations. These mutations prevent the body from transporting cholesterol and lipids (fats) into cells. As a result, a lipid called sphingomyelin builds up in cells to toxic levels, damaging tissues. NPC is a variable disease. Age of onset, specific symptoms, and symptom severity may vary from person to person. Potential symptoms may include:

• Fetal ascites (accumulation of fluid in the fetal abdomen)
• Cholestasis (impaired bile flow from the liver) which leads to jaundice (yellowing of the skin and eyes), failure to thrive, and growth deficiencies
• An enlarged liver and/or spleen
• Hypotonia (low muscle tone)
• Developmental delays
• Vertical gaze palsy (inability to move eyes up and down)
• Hearing loss
• Lack of muscle coordination
• An unsteady gait
• Seizures
• Cataplexy
• Sleep disturbances
• Behavioral difficulties
• Clumsiness
• Difficulty speaking (slurred and difficult-to-understand speech) or language regression
• Dysphagia (difficulty swallowing)
• Cognitive impairment
• Dementia

Improving outcomes in the NPC community depends on advancing research into treatments and ensuring access for those affected.