The Phase 3 PLEO-CMT clinical trial evaluated the safety, efficacy, and tolerability of PXT3003 for patients with Charcot-Marie-Tooth disease type 1A (CMT1A). Altogether, 323 people enrolled. During the trial, researchers compared 5mL high-dose PXT3003, low-dose PXT3003, and a placebo for a 15-month period. While the trial stopped early due to formulation problems, preliminary data highlighted an improvement in symptoms, with a placebo leading to worsening disease progression. PLEO-CMT-FU, an open-label extension, further confirmed safety and efficacy data. The higher dose correlated with more improvement.

Now, shares NeurologyLive, both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have asked for an additional study to further confirm the data. If the data is positive, PTX3003 has the potential to become the first approved therapy for those with CMT1A. Learn more about PTX3003.

Researchers are now doing so within the Phase 3 PREMIER trial, in which around 350 patients will enroll. This study will use the same high-dose PTX3003 as the PLEO-CMT study. Patients will receive either PTX3003 or a placebo, and will be evaluated over a 15-month period. The primary endpoint is any score changes on the ONLS, which measures functional motor disability. Data from the study should be available by the end of 2023. 

About Charcot-Marie-Tooth Disease type 1A (CMT1A)

Although Charcot-Marie-Tooth disease (CMT) is considered rare, it is also one of the most common inherited neurological disorders. CMT is also called hereditary motor and sensory neuropathy. There are multiple subtypes of CMT depending on the specific gene affected. However, in each case, the gene mutations cause peripheral nerve degeneration and inhibit muscle communication. In CMT1A, PMP22 gene mutations are the cause (most often a duplication). CMT1A is the most common CMT1 subtype. Symptoms and characteristics can (but do not always) include:

• High foot arch and hammertoes
• Difficulty running and/or walking
• Symmetrical muscle weakness and wasting in the feet and legs that may progress to the arms and hands
• Abnormal spinal curvature
• Numbness and tingling
• Balance difficulties
• Sleep apnea