Pharnext, CMT Association Partner on CMT1A Biomarkers to Support Phase 3 Study

Pharnext and the Charcot-Marie-Tooth Association (CMTA) have partnered to find new biomarkers associated with Charcot-Marie-Tooth disease type 1A (CMT1A), the most common subtype of the disease, according to a press release.

Its goal is to identify and validate CMT1A biomarkers that signal responses to treatment, and might serve to measure efficacy in future studies — starting with the Phase 3 trial of PXT3003 that Pharnext plans to open next year.

PXT3003 is a combination of three approved treatments — baclofen, naltrexone, and sorbitol — that act on three different receptors within the nervous system to limit the production of the PMP22 protein. Excessive amounts of PMP22, a feature of CMT1A, lead to the loss of the myelin sheath that coats and protects the nerve cells of the peripheral nervous system.

“This exciting collaboration between Pharnext and the Charcot-Marie-Tooth Association underscores the importance of involving patient advocacy organizations in better understanding the disease and working to bring new therapies to CMT1A patients,” said David Horn Solomon, CEO of Pharnext.

“Through this collaboration, we aim to further assess blood samples collected during our first Phase 3 trial of PXT3003 for novel biomarkers and notably confirm the potential of TMPRSS5 in CMT1A,” Solomon added.

TMPRSS5 is a recently identified CMT1A biomarker specific to the Schwann cells that produce myelin. Pharnext will screen blood samples collected from CMT1A patients enrolled in an earlier Phase 3 study, the PLEO-CMT trial (NCT02579759), in an effort to evaluate TMPRSS5 levels for monitoring treatment responses.

TMPRSS5 is one of a panel of potential biomarkers being examined, with a goal of identifying additional and previously unknown biomarkers of CMT1A.

“Results of this research collaboration might inform the addition of new exploratory endpoints in our next Phase 3 trial of PXT3003 to be initiated in [the first quarter of] 2021,” Solomon said. “We believe this alliance will enable us to accelerate our efforts in bringing a safe and effective therapeutic for this disease that currently has no viable treatment options.”

The CMTA also expressed optimism at the collaboration.

“As advocates for the CMT patient population, we are thrilled Pharnext is focusing its clinical development effort on CMT1A,” said Gilles Bouchard, chairman of the CMTA.

“Our collaboration with Pharnext aims to identify potential biomarkers for CMT1A which is crucial to better understand the pathophysiology of the disease, as well as to evaluate new therapeutic agents in future clinical trials. This could bring the CMT patient community a step closer to finding a treatment for this serious and debilitating disease for which there is currently no treatment available.”

PXT3003 was found to be safe, and to effectively eased disability compared with a placebo in 323 CMT1A patients with mild-to-moderate disease enrolled in the PLEO-CMT Phase 3 study, and its open-label extension PLEO-CMT-FU study (NCT03023540) in 187 patients.

But an unexpected issue with the highest dose formulation in one study group led to the trial’s high-dose arm being stopped early. The U.S. Food and Drug Administration (FDA) requested an additional pivotal Phase 3 trial to support a new application requesting PXT3003’s approval for CMT1A.

The FDA has previously granted PXT3003  orphan drug and fast track designations.