PTC Therapeutics Gains Momentum Through Novartis Agreement for Huntington’s Initiative

PTC Therapeutics Gains Momentum Through Novartis Agreement for Huntington’s Initiative

PTC Therapeutics Gains Momentum Through Novartis Agreement for Huntington’s Initiative

This week, PTC Therapeutics announced a significant agreement with Novartis to secure global rights for its oral candidate aimed at treating Huntington’s disease, known as PTC518. This splicing modifier targets the huntingtin protein HTT.

PTC518 is engineered to effectively cross the blood-brain barrier and reduce levels of the mutant HTT protein, which developers anticipate will greatly enhance the outcomes for individuals suffering from this rare neurodegenerative disorder, who presently have limited treatment alternatives.

The collaboration involves an initial payment of billion from Novartis to PTC. Should the company achieve specific development, regulatory, and sales targets, it stands to receive up to an additional .9 billion from the pharmaceutical giant, inclusive of various profit-sharing and royalty arrangements.

PTC has previously demonstrated success with its splicing technology, which played a crucial role in the FDA’s approval of risdiplam (Evrysdi) for spinal muscular atrophy in 2020. Currently, PTC518 is undergoing a phase 2 trial referred to as PIVOT-HD, with PTC sharing promising 12-month data in the summer.

The interim data from the trial indicated that participants receiving the highest dosage of the drug (10 mg) exhibited a reduction in the mutant huntingtin protein of up to 43%, alongside a sizeable slowing of motor symptoms—approximately 3.6 points on the TMS scale when compared to the placebo group. Importantly, the treatment candidate shows a favorable safety profile.

“Huntington’s Disease is a devastating, fatal, familial disease. This agreement with PTC is aimed at strengthening our neuroscience pipeline, showcasing our strategic focus and commitment to exploring new and potentially transformative treatments for neurodegenerative disorders with significant unmet needs,” remarked Vas Narasimhan, CEO of Novartis, in a statement.

“We are eager to leverage our neurodegenerative disease expertise and experience in HD to propel this promising first-in-class oral therapy forward for the Huntington’s disease community.”

A complex and challenging disease

Huntington’s disease is a rare, hereditary neurodegenerative condition impacting approximately 135,000 individuals globally. It stems from repeat expansion mutations in the huntingtin gene (HTT). Around 90% of cases are inherited dominantly, while the remaining 10% are believed to arise spontaneously.

The expression of the disease varies, influenced by the type of mutation and the number of trinucleotide repeats involved. Generally, symptoms appear during midlife and progressively worsen, often leading to complications that result in death within 10 to 30 years after diagnosis.

Treating Huntington’s disease has been particularly challenging, with numerous trials and possible therapies failing in later stages. For instance, Novartis had a Huntington’s treatment in progress called branaplam, which was halted in 2023 due to safety concerns, leading them to hope that the PTC collaboration will deviate from recent patterns in this field.

The agreement concerning Huntington’s disease provides a considerable advantage for PTC, especially following their announcement of unfavorable phase 2 results for utreloxastat in the treatment of amyotrophic lateral sclerosis (ALS) last week, as well as the closure of the ALS clinical trial program.