PTC Therapeutics announced this week that it has made a deal with Novartis for global rights to its oral Huntington’s disease candidate PTC518, a splicing modifier of the huntingtin protein HTT.
The drug is designed to cross the blood–brain barrier and lower levels of the mutant HTT protein, which developers hope will significantly improve outcomes for people affected by the rare, neurodegenerative disease who currently have few treatment options.
The deal includes an upfront payment of $1 billion from Novartis to PTC. If development, regulatory and sales milestones are met by the company then PTC will be eligible to receive up to $1.9billion more from the big pharma including various profit sharing and royalty payments.
PTC has already had success with its splicing platform, which led to the approval of risdiplam (Evrysdi) for treatment of spinal muscular atrophy by the FDA in 2020. PTC518, developed with the same platform, is currently being tested in a phase 2 trial called PIVOT-HD and the company reported good 12-month data in the summer.
The interim trial data showed reductions in the mutant huntingtin protein of up to 43% in those receiving the highest dose of the medication (10 mg) and a slowing of motor symptoms of approximately 3.6 points on the TMS scale versus placebo for the same treatment group. Notably, the safety profile for the candidate therapy appears to be good.
“Huntington’s Disease is a devastating, fatal, familial disease. 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 Vas Narasimhan, CEO of Novartis, in a press statement.
“We look forward to building on our expertise in neurodegenerative diseases and experience in HD with the intention to advance this potential first in class oral therapy for the Huntington’s disease community.”
A difficult disease to treat
Huntington’s disease is a rare, neurodegenerative genetic disorder affecting around 135,000 people around the world. It is caused by expansion repeat mutations in the huntingtin gene (HTT). Although around 90% of cases are inherited in a dominant fashion, 10% of cases are thought to occur spontaneously.
The disease is fairly heterogenous depending on a person’s mutation type and number of trinucleotide repeats present in their mutation, but it generally manifests in midlife and symptoms slowly worsen until the affected person dies from complications between 10 and 30 years after diagnosis.
Huntington’s has proved hard to treat with many trials and potential treatments failing at a late stage. For example, Novartis previously had another Huntington’s therapy in development, branaplam, but safety issues stopped its development in 2023. Novartis is doubtless hoping that PTC will buck recent trends in this area.
The Huntington’s deal is certainly a boost to PTC, which announced negative phase 2 results for utreloxastat for treatment of amyotrophic lateral sclerosis (ALS) last week, as well as a closure of the ALS trial program.