The French biotechnology company Pharnext faced a significant setback as its lead drug candidate PXT3003 failed to meet its primary endpoint in the Phase 3 PREMIER trial for Charcot-Marie-Tooth disease type 1A (CMT1A). The announcement triggered a dramatic collapse in the company's share value, though executives maintain hope for the program's future.
Trial Design and Outcomes
The PREMIER study evaluated PXT3003, a fixed-dose combination of baclofen, naltrexone, and sorbitol, in patients with CMT1A, the most prevalent form of the disease caused by mutations in the PMP22 gene. The trial's primary endpoint utilized the Overall Neuropathy Limitation Scale (ONLS) to measure functional disability.
The study's failure was attributed to an unexpectedly high placebo response, with control group patients showing improvement rather than the anticipated gradual decline. Pharnext argues that while ONLS remains a valid endpoint for long-term assessment, it may not be suitable for shorter-term clinical studies.
Safety Profile and Secondary Findings
Despite missing the primary endpoint, PXT3003 demonstrated a favorable safety and tolerability profile. Importantly, patients receiving the treatment showed no deterioration in their condition throughout the trial duration, which the company considers a positive indicator.
Disease Impact and Unmet Need
CMT1A, affecting approximately two-thirds of all CMT patients, is a progressive inherited condition characterized by peripheral nerve damage. While not typically fatal, the disease causes significant disability through muscle weakness, gait abnormalities, and numbness in extremities. Currently, no approved treatments exist for this condition.
Corporate Perspective and Future Plans
Hugo Brugière, Pharnext's manager, emphasized the broader context of the development program: "Although the results we are sharing today are not exactly what we had hoped for, they are nonetheless very promising." The company plans to leverage its decade-long data collection, including two Phase 3 studies and a six-year extension study, to support potential regulatory submissions.
Commercial Implications
The trial results may impact Pharnext's licensing prospects. Prior to the data release, the company had received three potential licensing offers valuing PXT3003 at up to €400 million. The company had strategically delayed signing any exclusive agreements pending the PREMIER trial results.
Ongoing Development
A parallel Phase 3 trial of PXT3003 conducted by Chinese partner Tasly is still ongoing, with results expected soon. Pharnext suggests that the totality of evidence, including this upcoming data, could still support a path forward for regulatory approval, particularly given the absence of other advanced-stage drug candidates for CMT1A.
