Funding Supports Pharnext’s Phase 3 Trial of PXT3003

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by Diana Campelo Delgado |

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PXT3003 for CMT1A

Pharnext has received €11 million ($13.3 million) in funding to support a Phase 3 trial investigating its investigational therapy PXT3003 for the treatment of Charcot-Marie-Tooth disease type 1A (CMT1A).

The proceeds include €6 million ($7.2 million) from existing shareholders and €5 million ($6 million) from European investors. The upcoming PREMIER trial (NCT04762758) is set to begin in March and to enroll 350 CMT1A patients at 50 sites around the world. More information about contacts and locations will be available here soon.

“We are pleased to announce this capital raise which demonstrates the strong continued support of our existing shareholders,” David Horn Solomon, PhD, CEO of Pharnext, said in a press release. “This funding will extend our cash runway to advance PXT3003 into the pivotal phase III trial in Charcot-Marie-Tooth disease Type 1A.”

In CMT1A, an extra copy of the PMP22 gene leads to excessive amounts of the PMP22 protein, resulting in the loss of the myelin coating that protects and helps nerve cells of the peripheral nervous system send electrical signals more efficiently.

PXT3003 is a combination of three approved treatments — baclofen, naltrexone, and sorbitol — that act on three different receptors in the nervous system to limit the production of PMP22, ultimately resulting in increased myelination.

The investigational therapy has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, as well as fast track status from the FDA.

The safety and effectiveness of PXT3003 in CMT1A patients have been demonstrated in the PLEO-CMT Phase 3 clinical trial (NCT02579759) and its open-label extension PLEO-CMT-FU study (NCT03023540).

PLEO-CMT involved 323 patients with mild-to-moderate CMT1A, ages 16 to 65, who were assigned randomly to receive either a low or high dose of PXT3003, or a placebo, given as an oral solution twice daily for 15 months. After completing the trial, 187 participants entered the extension study, in which all received PXT3003 for nine months.

The Phase 3 trial met its primary goal, with patients on the highest dose of PXT3003 showing meaningful reductions in their Overall Neuropathy Limitation Scale (ONLS) scores — a measure of disability — compared with those on a placebo, as well as better walking speed.

However, an unexpected issue with the high dose formulation led to a treatment interruption that lasted five months on average. The missing data resulting from that temporary discontinuation lead the FDA to request an additional pivotal Phase 3 trial to support PXT3003’s approval for CMT1A.

PREMIER will be similar to PLEO-CMT in many ways. Patients also will have mild-to-moderate CMT1A, ages ranging from 16 to 65, and receive their assigned treatment for 15 months.

Participants will be assigned to receive either high dose PXT3003 or a placebo. For this trial, the manufacturing issue with the high dose has been resolved, and the medication now will be delivered in a greater volume of liquid, packaged into sachets, to simplify and improve dosing accuracy.

The trial’s main goal is to assess changes in the extent of physical disability among participants, as measured by ONLS scores from study start to month 15. Secondary goals include changes in walking speed, muscle strength, perceived disease severity, and disease-related impairment. Safety and tolerability also will be monitored throughout the study.

In the meantime, Pharnext continues to explore the long-term safety and effectiveness of PXT3003 in the PLEO-CMT-FU trial. Among the initial 187 patients, 130 are still receiving the high dose formulation in this open-label extension study and had been followed for more than two years.

The company plans to report top-line data from this trial in the coming months.