PTC Therapeutics have announced the initial results of their Phase 3 MOVE-FA trial of vatiquinone (PTC-743) in people with FA. Vatiquinone targets an enzyme called 15-lipoxygenase, which is a regulator of energetic and oxidative stress pathways that are disrupted in FA. Although the trial did not reach its primary endpoint, which is the main measurement to show whether the drug works, PTC Therapeutics did observe meaningful clinical benefit in some of the trial’s other endpoints. Therefore, they plan to discuss a potential path forward with the drug regulators in the US and EU.
During the trial, which enrolled 146 children and adults with FA, participants received either vatiquinone or a placebo three times a day for 72 weeks. The primary endpoint was a statistically significant change in the overall mFARS score at 72 weeks in participants aged 7-21 years (primary analysis population, 123 people). The mFARS is a clinical rating scale which measures FA progression and is made up of four components. These are: bulbar function (which assesses coughing and speech), upper limb coordination (which assesses tremor and coordination of arms and hands), lower limb coordination (which assesses coordination of legs and feet), and upright stability (which assesses ability to stand and walk).
Although the study did not achieve its primary endpoint as there was not a statistically significant change in the overall mFARS score, PTC Therapeutics did observe meaningful clinical benefit in some components of mFARS. There was a slowing of progression in both bulbar and upright stability components at 72 weeks. There were also improvements in the impact of fatigue with vatiquinone treatment compared to placebo.
As the trial was conducted during the Covid-19 pandemic, there was some disruption in how the trial could be conducted in a number of participants. Because of this PTC also analysed the data to only include participants who completed the trial on the assigned therapy without disruption. When analysing this population (called the primary analysis population completers), vatiquinone showed a greater effect on FA progression, with the drug slowing disease progression by 75%.
As there is evidence of meaningful clinical benefit and a high unmet need for a treatment for children with FA, PTC Therapeutics plan to discuss a potential path to try and get the drug approved with the drug regulators in the US and EU.
In addition to their trial results, PTC Therapeutics have also recently announced that they are discontinuing their preclinical and early research programmes in gene therapy. This includes their preclinical gene therapy programme for FA. This decision was taken as part of their strategic portfolio prioritisation.