PXT3003 Shows Sustained Safety, Benefits for Patients With CMT1A

High-dose PXT3003, an investigational therapy for Charcot-Marie-Tooth disease type 1A (CMT1A), continues to show long-term safety and efficacy, according to an early analysis of a Phase 3 extension study.

All participants showed improvements on the Overall Neuropathy Limitation Scale (ONLS), a measure of physical disability.

“These new results from the interim analysis of the ongoing open-label Phase 3 extension study show very promising safety and efficacy data of PXT3003 in CMT1A after more than four years of treatment,” Florian P. Thomas, MD, PhD, the study’s lead investigator in the U.S., said in a press release.

“It reinforces our hope that PXT3003 could be the first treatment approved for patients suffering from this debilitating disease,” he added.

The PLEO-CMT-FU extension study (NCT03023540) enrolled 187 individuals, ages 16 to 67, who had previously participated in the main PLEO-CMT study (NCT02579759).

That original study evaluated PXT3003’s safety and efficacy, comparing a low dose and a high dose of the therapy candidate, given as an oral solution twice a day. An expected issue in the high dose formulation made Pharnext, the treatment’s developer and the sponsor of both studies, stop this group in September 2017. This meant that the initial high dose was then given in twice the volume of the low dose formulation.

Patients receiving the high dose showed the greatest improvement in ONLS scores, which measure limitations in the everyday use of a person’s arms and legs. Those treated with a placebo during the main portion of the study had shown ONLS declines. They then improved, however, over the extension phase with PXT3003 treatment. Participants receiving PTX3003 for the duration showed ONLS improvements throughout the two phases.

The combined trials have now been running for approximately 4.5 years.

“Although these new data were generated from an open-label study” — meaning both researchers and participants are aware of the treatment being given — “the findings are consistent with the safety and efficacy results of PXT3003 observed in prior clinical studies in CMT1A,” said Adrian Hepner, MD, PhD, chief medical officer of Pharnext.

“In addition,” Hepner said, “the fact we have just initiated the PREMIER trial in a similar patient population, using the same High Dose of PXT3003 and measuring the same efficacy endpoint [goal] ONLS, reinforces our confidence in the potential positive outcome of our ongoing pivotal Phase 3 study.”

PXT3003 is a combination of baclofen, naltrexone, and sorbitol, three approved therapeutic compounds meant to boost the body’s production of myelin by limiting the production of the PMP22 protein that is overproduced in people with CMT1A. Myelin insulates nerve signals from being lost during transmission. It is the loss of myelin, which serves as a protective coating around nerves, that underlies CMT1.

Pharnext recently enrolled the first patient in the Phase 3 PREMIER study (NCT04762758). Similar to the PLEO-CMT trial, PREMIER will compare the safety and efficacy of PXT3003 with a placebo, over 15 months of treatment. The trial will be conducted in the U.S., Canada, Europe, and Israel. Information on contacts and locations can be found here.

The company initiated this trial at the request of the U.S. Food and Drug Administration, following a manufacturing problem that led to missing data in PLEO-CMT when treatment had to be interrupted.