Editorial note: This post refers to Pharnext and its experimental CMT1A therapy PXT3003. Pharnext is no longer operating, and PXT3003 is not an approved or available treatment. We have kept this post as part of our historical record.

The PREMIER trial, initiated in March 2021, is an international, randomized, double-blind, two-arm, placebo-controlled, pivotal Phase III study. Its primary objective is to evaluate the efficacy and safety of PXT3003 versus placebo in patients with mild-to-moderate CMT1A (the most common genetic subtype of Charcot-Marie-Tooth disease) over a 15-month period. The dose of PXT3003 tested in PREMIER corresponds to the high dose (HD) tested in the prior Phase III clinical study, PLEO-CMT, and its ongoing open-label extension, PLEO-CMT-FU. As agreed with regulatory agencies, the primary efficacy endpoint is the Overall Neuropathy Limitations Scale (ONLS), which measures functional motor disability.

A total of 387 patients with mild-to-moderate CMT1A were enrolled in the PREMIER trial, exceeding the initial enrollment target of 350 participants: 153 in the United States, 183 in Europe, 39 in Canada, and 12 in Israel.

The 15-month double-blind phase is followed by an open-label extension phase called PREMIER-OLE. All patients who completed the double-blind phase are eligible to join PREMIER-OLE and have the opportunity to receive PXT3003 HD until the treatment becomes commercially available, should PXT3003 be approved by the FDA and the EMA, respectively. The first patient entered the PREMIER-OLE phase in September 2022.

Pharnext also successfully completed the manufacturing transfer and scale-up of PXT3003 from Unither’s facility in Colomiers, France, to Unither’s facility in Rochester, New York, in preparation for potential marketing authorization. PXT3003 can now be manufactured in batches of up to 3,500 liters of oral solution, a volume potentially compatible with a commercial supply chain and offering a more convenient, flexible form for CMT1A patients.

Topline results from the PREMIER trial were planned for announcement in Q4 2023.