RARE Daily

PTC Reports Positive Interim Phase 2 Results on HD Therapy, FDA Lifts Partial Clinical Hold

June 21, 2024

Rare Daily Staff

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

PTC said that the FDA has lifted the partial clinical hold on the program based on review of the PIVOT-HD data.

Huntington’s disease (HD) is a rare, hereditary, genetic disorder of the central nervous system. It is caused by a defective gene. This gene produces a protein, called Huntingtin, which is involved in the functioning of the nerve cells in the brain (neurons). When the gene is defective, it produces an abnormal (or mutated) Huntingtin protein that is toxic and causes neuron damage and neuron death.

HD usually presents in people who are in their 30s or 40s. Symptoms can present earlier in life, and this is called the Juvenile HD. There are also cases of infantile HD, when symptoms develop in children who are younger than 10 years old. 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, currently, there is no cure for HD and there are no approved drugs that delay the onset or slow disease progression.

PTC is developing a potential treatment for Huntington’s disease based on its splicing platform technology. PTC518, a small molecule that can be taken orally, reduces the production of the mutated Huntingtin protein that leads to injury and death of the neuron, which results in disease progression. The orally bioavailable small molecule penetrates the blood brain barrier, is selective, titratable, and not effluxed, which are key differentiation properties.

At Month 12, PTC518 treatment resulted in dose-dependent lowering of mutant huntingtin (mHTT) protein in the blood and cerebrospinal fluid (CSF) in the interim cohort of patients. In addition, favorable trends were demonstrated on several relevant HD clinical assessments including Total Motor Score (TMS) and Composite Unified Huntington’s Disease Rating Scale (cUHDRS). Furthermore, following 12 months of treatment, PTC518 continues to be safe and well tolerated.

“The evidence of both CNS biomarker and early clinical effects at Month 12 along with the continued favorable tolerability profile supports the promise of PTC518 to address the need for an effective and safe disease-modifying therapy for patients living with Huntington’s disease,” said Matthew Klein, CEO of PTC Therapeutics. “With these data in hand, we look forward to the next steps in the PTC518 development program.”

Photo: Matthew Klein, CEO of PTC Therapeutics

Stay Connected

Sign up for updates straight to your inbox.