New Orphan Drug Designation - PBT2 for Treating Cognitive Decline in Huntington's Disease

RDR Staff

Prana Biotechnology announced the US Food and Drug Administration (FDA) has granted orphan drug designation to their drug PBT2 for the treatment of Huntington Disease. The company plans to apply for orphan drug designation in Europe and other jurisdictions.

Huntington’s disease
is a genetic neurodegenerative disorder in which patients are fine until the age of about 30 then their muscle control deteriorates.  Much of the neuronal degeneration occurs in the cerebral cortex and basal ganglia, which play a key role in movement, cognition, and behavior. The cumulative damage to these areas results in the hallmark symptoms of chorea (uncontrollable, jerky movements), neuropsychiatric symptoms, loss of executive functioning and dementia. At present there is no cure or means to delay progression and treatment is limited to easing the chorea-like symptoms. More than 30,000 people in the U.S. have Huntington disease.

PBT2 is designed to treat the cognitive problems seen in patients with Huntington’s disease. Prana Chairman and CEO Geoffrey Kempler said, "The FDA's decision to grant Orphan Drug designation is a reflection of the high unmet need for neurological drugs that can slow, halt or improve the decline of cognition and allow sufferers to have a better quality of life."

In February,  Prana announced the results from their phase 2 clinical trial that randomly assigned 109 patients with Huntington’s disease to receive 0 mg, 250 mg, or 100 mg of PBT2 for 26 weeks.

The study found the primary endpoints of safety and tolerability were met (no statistically significant differences in adverse events in the 3groups). Furthermore, secondary efficacy endpoints showed there was a significant improvement in a measure of executive function (Trail Making Test Part B) in patients receiving the 250 mg dose. More specifically, the company reported that theTrail Making Test Part B (e.g., the ability to plan activities) in the 250mg dose group was improved compared to placebo at both 12 (p<0.001) and 26 weeks (p=0.042).

In addition to the above,  exploratory brain imaging analysis of 6 patients in the phase 2 study may indicate that PBT2 can attenuate brain atrophy that occurs in Huntington’s disease.  Two patients receiving placebo and 4 patients receiving PBT2 were involved in the brain imaging sub-study and preliminary analysis indicates the patients taking PBT2 had less brain atrophy in areas of the brain known to be atrophied in Huntington’s disease (compared to the 2 patients not receiving PBT2).

Dr Diana Rosas, Associate Professor of Neurology at Harvard Medical School and the study’s co-Principal Investigator who conducted the imaging sub-study commented: “Despite the very small number of patients in the sub-study, the data are suggestive of a beneficial effect of PBT2 in regions of the brain that are known to be vulnerable to Huntington disease.” 

Prana is preparing its Post Phase 2 Trial dossier for submission to the FDA to commence discussions on the next development steps for PBT2.
MRI image of Huntington’s disease patient showing brain atrophy courtesy Wikimedia commons.
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