First European CMT1A Patient Enrolled in PREMIER Trial

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by Forest Ray PhD |

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PREMIER Phase 3 trial PXT3003

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Pharnext has enrolled the first patient in Europe for its Phase 3 clinical trial of PXT3003, an investigational therapy for Charcot-Marie-Tooth disease type 1A (CMT1A).

The international PREMIER trial (NCT04762758) is already underway in the United States, where the first patient was dosed earlier this year.

“We are delighted to see the ongoing progress in the enrollment of the PREMIER trial through the opening of the first European center in Marseille [France] according to plans,” Adrian Hepner, MD, PhD, Pharnext’s chief medical officer, said in a press release.

“The addition of European centers to those already running in the U.S. represents another positive step for PXT3003 as we seek to help patients with CMT1A,” he added. “Additional centers will also be activated worldwide over the summer.”

This first European patient was enrolled at the University Hospital La Timone in Marseille.

The study continues to recruit participants with mild-to-moderate CMT1A across several of its sites in the U.S. and remains on track to complete enrollment of approximately 350 people by the second quarter of 2022. Besides locations in European countries, the trial also will be conducted in Canada and Israel.

Participants will be assigned randomly to receive either PXT3003 or a placebo, which they will take as an oral solution twice daily with food over 15 months.

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The study’s main goal is to assess changes in the extent of physical disability as measured by the Overall Neuropathy Limitation Scale. Other goals include periodic evaluations of the medication’s safety and tolerability, changes in participants’ walking ability and muscle strength, and self-reported measures of disease severity.

Top-line results from PREMIER are expected in the third quarter of 2023.

Pharnext hopes to be able to apply for marketing authorization in both the U.S. and Europe early in 2024, assuming that both the PREMIER trial and a preclinical study in a CMT1A rat model meet their goals.

The PREMIER trial recently received financial support from Alpha Blue Ocean, through a financing agreement for up to €81 million (roughly $95.6 million).

“I’m honored to lead the first site in Europe to enroll patients in this promising pivotal Phase III clinical study, another step towards a potential treatment for those with CMT1A,” said Shahram Attarian, MD, PhD, lead investigator of the PREMIER trial in Europe. “I look forward to having more sites enrolling subjects in Europe, and globally, in the coming weeks.”

PXT3003 is designed to increase patients’ myelin — a fatty coating that insulates nerves to prevent signal loss — by reducing the excessive PMP22 protein levels associated with CMT1A. The medication is a combination of the three approved treatments baclofen, naltrexone, and sorbitol.

In PLEO-CMT (NCT02579759), a prior Phase 3 study, PXT3003 was found safe and effective. Patients given the same dose of PXT3003 to be used in PREMIER had meaningful decreases in their ONLS scores compared with those on a placebo, as well as superior walking ability.

However, that trial had missing data due to a manufacturing issue and a temporary treatment interruption, leading the U.S. Food and Drug Administration to request an additional Phase 3 study.