The decision to launch this new clinical trial was based on recommendations given by the U.S. Food and Drug Administration (FDA) after completing preliminary review and discussion of the pivotal Phase 3 PLEO-CMT study.
Despite the positive results of PLEO-CMT, the high-dose arm of the study was terminated early because of an “unexpected intercurrent formulation event” in one of the study groups, according to Pharnext. Based on this, the regulatory agency recommended that Pharnext run an additional trial to gather data that could ultimately support without doubt a New Drug Application for PXT3003 in CMT1A.
“The FDA acknowledged that CMT1A is a disease with high unmet medical need, granting Fast Track designation for PXT3003 in February 2019, and encouraged the Company to return to discuss a proposed study design,” Pharnext stated in a press release.
PXT3003 results from the combination of fixed doses of baclofen, naltrexone, and sorbitol — three already-approved medicines that act on the nervous system. The combo therapy is formulated to be administrated as an oral solution given twice a day.
The therapy has been granted orphan drug designation in the European Union and the United States, and priority review in China.
Preclinical studies demonstrated that PXT3003 can inhibit abnormally high levels of the PMP22 gene, the duplication of which causes CMT1A. It also increased the amount of the protective myelin layer around peripheral nerves, relieving neuromuscular symptoms associated with the disease.
The pivotal, double-blind PLEO-CMT trial (NCT02579759) was designed to assess the safety and efficacy of PXT3003 in 323 CMT1A patients, ages 16–65. The treatment was well-tolerated and eased disability compared with placebo in patients with mild to moderate disease.
Participants who completed the 15-month course of treatment in this Phase 3 trial will have the possibility to roll over to an extension study, the PLEO-CMT-FU (NCT03023540), to continue treatment with PXT3003 until it is commercially available. This ongoing study will provide long-term safety and efficacy data for PXT3003.
“We remain strongly confident in the potential of PXT3003 as a much-needed therapeutic option for patients with CMT1A, particularly given the consistent signal of efficacy observed across the clinical studies already performed and PXT3003’s strong safety profile to date,” Daniel Cohen, MD, PhD, co-founder and CEO of Pharnext, said. “We are fully committed to aligning with the FDA on the design of a clinical study as quickly as possible, in order to bring PXT3003 to U.S. patients with CMT1A.”
Pharnext is also continuing the development program for PXT3003 in CMT1A in Europe and China. The company is working to advance the registration path in Europe, and pursuing a development and registration path through its Chinese pharmaceutical partner, Tasly.