Pharnext Enrolls 1st Patient in PREMIER Trial Testing PXT3003 for CMT1A

The first patient has been enrolled in a pivotal Phase 3 trial testing Pharnext’s investigational therapy PXT3003 for Charcot-Marie-Tooth disease type 1A (CMT1A), the company announced.

Called PREMIER (NCT04762758), the trial intends to recruit approximately 350 patients, ranging in age from 16 to 65, with mild to moderate CMT1A — the most common disease type, accounting for about two-thirds of all cases. The trial is recruiting across 50 clinical sites in the U.S., Canada, Europe, and Israel.

According to Pharnext, which is sponsoring the trial, the first patient was enrolled at the Austin Neuromuscular Center, in Texas. The other site already recruiting participants is Oregon Neurology, in Springfield, Oregon. More information about contacts and about the sites yet to open can be found here.

‘The PREMIER trial is an important milestone for those suffering from this debilitating disease and it is encouraging to see the first patient being dosed at a U.S. center,” said Mario Saporta, MD, PhD, director of the CMT Center of Excellence at the University of Miami’s Miller School of Medicine and lead investigator of the PREMIER trial in North America.

The company, which is continuing to monitor and comply with regulatory guidance during the COVID-19 pandemic, expects the other sites to open soon.

“I look forward to seeing the patients being dosed in the PREMIER trial across European centers over the coming weeks,” said Shahram Attarian, MD, PhD, the trial’s lead investigator in Europe and a coordinator of the FILNEMUS Rare Diseases Network and Neuromuscular Diseases Reference Centers in France.

“This is an essential step forward for PXT3003 and developing an accessible potential treatment for patients suffering from CMT1A,” said Attarian, head of the neuromuscular diseases and ALS department at the University Hospital La Timone in Marseille, in France.

People with CMT1A have a duplicated PMP22 gene, which leads to the excessive production of the PMP22 protein. That, in turn, causes a loss of the myelin coating that protects the nerve cells of the peripheral nervous system — which connects the brain and spinal cord to the body’s limbs and organs — and helps them send electrical signals more effectively.

PXT3003 is a combination of three approved treatments — baclofen, naltrexone, and sorbitol — intended to limit the production of PMP22 and boost the production of myelin.

In the PREMIER trial, participants will be assigned randomly to receive either a high dose of PXT3003, or a placebo, given as an oral solution twice daily for 15 months.

The study’s main goal is to assess changes in the extent of physical disability with treatment, as measured with the Overall Neuropathy Limitation Scale (ONLS). The total ONLS scores range from zero, or no disability, to 12, noting maximum disability.

Additional (secondary) goals include changes in walking ability and muscle strength, as well as patients’ perceived disease severity and disease-related impairment. The therapy’s safety and tolerability also will be monitored.

If the PREMIER trial achieves its primary goal, and promising results are seen in an animal model of CMT1A, Pharnext plans to seek the therapy’s approval for this disease subtype by submitting an application to the U.S. Food and Drug Administration and a marketing authorization to the European Medicines Agency.

In a previous Phase 3 trial, called PLEO-CMT (NCT02579759), PXT3003 was found safe and effective. Participants given the same high dose of PXT3003 to be used in PREMIER showed meaningful reductions in their ONLS scores compared with those on a placebo, as well as better walking ability.

However, PLEO-CMT had missing data due to a manufacturing problem and a temporary treatment interruption, leading the FDA to request an additional Phase 3 trial.

Pharnext received €11 million ($13.3 million) in funding from existing shareholders and European investors to support this Phase 3 trial.

All participants were allowed to enroll in the PLEO-CMT-FU extension study (NCT03023540), which is assessing the long-term safety and effectiveness of PXT3003.

“PXT3003 has already shown an encouraging response in our prior Phase II and Phase III (‘PLEO-CMT’) trials using the ONLS, and we place high hope that the efficacy and safety of PXT3003 will be further demonstrated in our PREMIER trial,” said Adrian Hepner, MD, PhD, chief medical officer of Pharnext.

“CMT1A is a severe, debilitating, chronic inherited neuropathy representing a serious unmet medical need and the initiation of the PREMIER trial shows we are now on a clear path forward for PXT3003 as we seek to help patients,” he added.