Phase 2 data from PTC Therapeutics showed that the Novartis-partnered Huntington’s disease asset slowed progression by more than 50%. Analysts say the decision to initiate a last-stage trial reflects a lack of confidence in an accelerated FDA nod.
Following encouraging mid-stage data, Novartis and PTC Therapeutics have decided to advance their Huntington’s disease candidate into late-stage development—a move that analysts say demonstrates the partners’ confidence in the program but also their apprehension around the likelihood that the FDA will grant accelerated approval based on existing data.
The decision to start Phase 3 development was driven by an interim readout from the long-term extension phase of the mid-stage PIVOT-HD study presented on Tuesday.
A 5-mg dose of PTC and Novartis’ drug, called votoplam, slowed disease progression by 28% at 24 months, as compared with natural history controls. Votoplam’s benefits were more pronounced at the 10-mg dose, which reduced worsening by 52%. Prolonged votoplam treatment also kept neurofilament light chain levels suppressed below baseline through 24 months of follow-up.
Bolstered by these data, Novartis said on an earnings call Tuesday that it has launched the Phase 3 INVEST-HD study of votoplam, testing the drug against placebo in patients with Huntington’s disease. The trial aims to enroll 770 patients, with a readout expected in 2030, according to the pharma’s presentation.
While Novartis will take charge of votoplam’s late-stage development, PTC will work with the pharma to discuss existing data and determine next steps for the asset, “including regulatory actions,” according to the biotech’s Tuesday release.
The initiation of INVEST-HD “conveys continued long-term optimism around the program,” analysts at RBC Capital Markets told investors in a Tuesday note, however Novartis and PTC are being “deliberately measured” regarding their regulatory plans, offering no specific mention of accelerated approval.
This ambivalence, the analysts continued, “may also suggest a view that the existing dataset . . . may still not be wholly conclusive.”
Votoplam is a small-molecule splicing modifier that works by introducing a stop codon into the mRNA molecule for the huntingtin protein, a defective form of which is upregulated in patients with Huntington’s disease. Originally developed by PTC, votoplam was partnered with Novartis in December 2024 for $1 billion upfront and up to $1.9 billion in milestones.
Under this partnership, PTC is responsible for moving votoplam past PIVOT-HD, after which Novartis would take over and run the asset’s late-stage program. PTC is entitled to a 40% share of the drug’s U.S. profits plus double-digit tiered royalties on international sales.
