RARE Daily

PTC Report Positive Interim Data from Experimental Drug Trial in Huntington’s Disease Patients

June 21, 2023

Rare Daily Staff

PTC Therapeutics reported positive interim data from the 12-week portion of its PIVOT-HD phase 2 study of its experimental therapy PTC518 in the rare, neurodegenerative condition Huntington’s disease.

The company said the study demonstrated dose-dependent lowering of Huntingtin (HTT) protein levels in peripheral blood cells, reaching a mean 30 percent reduction in mutant HTT levels at the 10mg dose level. In addition, PTC518 exposure in the cerebrospinal fluid was consistent with or higher than plasma unbound drug levels.

Huntington’s disease (HD) is a rare, hereditary, genetic disorder of the central nervous system. It is caused by a defective gene that produces a mutated form of the protein Huntingtin, which is involved in the functioning of the neurons in the brain. Huntingtin protein that is toxic and causes neuron damage and neuron death. While symptoms vary from person to person, the disease primarily affects the brain and results in abnormal movements, difficulties with speech, swallowing, and walking, as well as a number of other symptoms including behavioral, cognitive, and motor symptoms. While there are therapies approved for specific disease symptoms, there is no cure for HD and there are currently no approved drugs that delay the onset or slow disease progression.

PTC518 is PTC’s experimental, small molecule drug that can be taken orally, reduces the production of the mutated Huntingtin protein. The small molecule drug penetrates the blood brain barrier.

PIVOT-HD is a global, placebo-controlled study and consists of two parts: an initial 12-week placebo-controlled phase focused on PTC518 pharmacology and pharmacodynamic effect, followed by a 9-month placebo-controlled portion. The study will initially include two dose levels.

The data shows that PTC518 treatment was also demonstrated to be well tolerated, with no treatment-related serious adverse events, no reports of peripheral neuropathy or dose-limiting toxicities. Furthermore, there were no CSF neurofilament light chain protein (NfL) treatment-related spikes, with an overall trend towards lowering of CSF NfL levels following 12 weeks of PTC518 treatment.

“We are very pleased with the encouraging data from the PIVOT-HD interim analysis demonstrating dose-dependent HTT lowering, desired CSF exposure and a favorable tolerability profile without evidence of treatment-related serious adverse events or CSF NfL spikes,” said Matthew Klein, CEO of PTC Therapeutics.

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