Rare Daily Staff

Pharnext reported positive topline results from its pivotal late-stage clinical trial evaluating two doses of its experimental drug PXT3003 for the treatment of Charcot-Marie-Tooth (CMT) type 1A disease, a group of inherited, progressive, chronic peripheral neuropathies.

CMT type 1A is the most common form of CMT, a rare disease that causes degradation of the neuronal sheath and nerve dysfunction. As a result, patients suffer from progressive muscle atrophy of the limbs causing problems with walking, running, balance, and hand function. At least 5 percent of patients need wheelchairs. They may have loss of sensation and pain. First symptoms usually appear during childhood and progress throughout patients’ lives. To date, no curative or symptomatic medications have been approved and treatment consists of supportive care such as orthotics, leg braces, physical and occupational therapy or surgery.

The pivotal, 15-month, double-blind phase 3 study assessed the efficacy and safety of PXT3003 compared to placebo for the treatment of patients with mild to moderate CMT1A. The study evaluated two doses of PXT3003, and patients were randomized 1:1:1. The study enrolled 323 patients aged 16 to 65 years in 30 sites across European Union, United States, and Canada. The primary endpoint was the Overall Neuropathy Limitation Scale (ONLS) measuring patient disability. A reduction of 0.3 point on this scale was determined to be meaningful according to previously described methodology.

The three groups had comparable characteristics at baseline. For endpoint analysis, there were 87 patients in placebo, 93 patients in lower dose and 55 patients in higher dose arms at baseline. The lower number of patients in the higher dose is due to unexpected formulation and stability issues. The results showed a mean reduction of 0.4-point ONLS observed in the higher dose group. The secondary endpoints confirmed the superiority of the higher dose, in particular the improvement on the 10-meter walk test with a reduction of 0.5 seconds.

PXT3003 was safe, well tolerated and showed a similar safety profile as seen in the phase 2 study. Regulators in the United States and European Union have previously granted PXT3003 Orphan Drug designation.

The study is the first to provide evidence of PXT3003 providing a meaningful improvement of CMT1A patients in showing a statistically significant amelioration on the ONLS disability scale. Based on these results, Pharnext intends to file for market approval in the United States and European Union.

“We are thrilled with the outcome of the trial and with the clearly demonstrated efficacy of PXT3003 in addressing the debilitating disease progression of CMT1A,” said Professor Daniel Cohen, Pharnext’s co-founder and CEO. “These results validate the broad potential of our Pleotherapy drug discovery platform in other neurodegenerative and other disorders and, of course, represent a tremendous milestone for Pharnext.”

October 16, 2018
Photo: Daniel Cohen, CEO of Pharnext