Novartis and PTC Therapeutics have announced a collaboration to advance the development of PTC518, an investigational oral small molecule for Huntington's disease. The agreement, potentially worth up to $2.9 billion, aims to leverage PTC's splicing platform to target the underlying cause of Huntington's disease, offering a new approach to treating this neurodegenerative disorder.
Targeting Mutant Huntingtin Protein
PTC518 is designed to reduce levels of mutant Huntingtin (mHTT) protein, which is responsible for the progressive degeneration of nerve cells in the brain. Interim results from the Phase II PIVOT-HD trial (NCT05358717) have demonstrated durable, dose-dependent reductions in mHTT levels in both blood and cerebrospinal fluid (CSF). At 12 months, patients dosed with 10 mg of PTC518 showed a 1.33% change from baseline, while those dosed with 5 mg showed a 2% reduction, compared to a 4.9% reduction in placebo patients. These early results also suggest potential dose-dependent benefits on key clinical measurements.
Novartis' Commitment to Neuroscience
"This agreement with PTC is intended to bolster our neuroscience pipeline and reflects our strategic focus and commitment to explore new and potentially transformative approaches for neurodegenerative diseases with high unmet needs," said Novartis CEO Vas Narasimhan, MD. Novartis plans to assume oversight of the development, manufacturing, and commercialization of PTC518 after the completion of the PIVOT-HD trial, expected in the first half of 2025.
This collaboration marks Novartis' return to the Huntington's disease therapeutic area after halting development of branaplam in February 2023 due to clinical setbacks. The company had previously suspended dosing of branaplam in adults with Huntington's disease in the Phase IIb VIBRANT-HD trial (NCT05111249) following concerns about peripheral neuropathy.
Financial Terms and Future Plans
Under the terms of the agreement, Novartis will pay PTC $1 billion upfront and up to $1.9 billion in milestone payments tied to development, regulatory, and sales achievements. PTC will retain a 40% share of U.S. profits and losses, with Novartis receiving the remaining 60%. The collaboration is expected to close in the first quarter of 2025, pending regulatory clearance.
PTC Therapeutics CEO Matthew B. Klein, MD, stated, "We are excited to collaborate with Novartis to accelerate the potential of PTC518 for the hundreds of thousands of HD patients worldwide in need of a therapy designed to be well-tolerated and an effective disease-modifying therapy."
Huntington's Disease Treatment Landscape
Huntington's disease is a genetic disorder that causes progressive degeneration of nerve cells in the brain, leading to motor, cognitive, and psychiatric symptoms. Current treatments primarily address the symptoms of the disease, with no approved therapies to delay onset or slow progression. PTC518 represents a potential disease-modifying approach by targeting the underlying cause of the disease.
Analyst Perspective
William Blair analyst Sami Corwin noted that the deal validates PTC518 and PTC's splicing platform, adding that Novartis' experience in developing drugs for CNS-based diseases could accelerate the clinical development and bolster the commercialization of PTC518. Corwin also highlighted the potential for accelerated approval based on positive regulatory discussions with the FDA, given the high commercial potential of a small molecule therapy compared to other modalities.
