PXT 3003 fails in Phase III trial forCharcot-Marie-Tooth disease type 1A due to placebo effect

Pharnext has unveiled topline results of a Phase III study (called PREMIER) of PXT 3003, its drug candidate in Charcot-Marie-Tooth disease type 1A (CMT1A), a genetic disorder caused by a duplication of the PMP22 gene which affects the peripheral nerves, resulting in muscle weakness and potentially sensory loss.

The drug is a fixed-dose combination of baclofen, naltrexone and sorbitol formulated as an oral solution given twice a day and the three individual components of PXT 3003 were selected to downregulate the overexpression of PMP22 protein.

The results are disappointing. On the overall neuropathy limitation scale (ONLS), which measures functional motor disability, patients receiving the candidate with mild-to-moderate CMT1A experienced improvement, rather than the slow deterioration typical of CMT1A’s natural progression, but so did those receiving placebo. The Paris-headquartered group said: "This unexpected improvement in the placebo group complicates the interpretation of the results based on this endpoint [and] also confirms what the medical literature as a whole has been saying for many years, namely that ONLS is undoubtedly a relevant endpoint over the long term, but not over such a short period of time as a clinical study."

Pharnext plans to continue analyzing the data, "particularly in collaboration with potential partners for licensing or acquisition of PXT 3003." At the end of November, the company confirmed that it had received "three offers to date, including one binding and two non-binding, from pharmaceutical companies [which] based on the latest discussions with the candidates, these offers would generate a cash flow for Pharnext of up to €400 million, excluding royalties indexed to sales of the future drug."