Pharnext working toward applications for PXT3003 approval

Company analyzing clinical trial data of therapy candidate to treat CMTA1

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Pharnext is analyzing clinical trial data that could support applications to approve PXT3003, its therapy candidate for people with Charcot-Marie-Tooth type 1A (CMT1A), in the U.S. and Europe.

“We remain hopeful of finally being able to bring a medical solution to patients with no treatment,” Hugo Brugière, manager of Pharnext, said in a company press release.

The latest developments come on the heels of top-line data from the pivotal Phase 3 PREMIER clinical trial (NCT04762758), which tested the effectiveness and safety of PXT3003.

PXT3003 is an oral medication made up of baclofen, naltrexone, and D-sorbitol. All three compounds work by lowering PMP22 protein levels in different ways, improving neuromuscular function.

The PREMIER trial included 387 patients with mild-to-moderate CMT1A, ages 16 to 65, from multiple centers across the U.S., Canada, Europe, and Israel. Participants were randomly assigned to receive either oral PXT3003 twice a day or a placebo, for 15 months.

Changes in disability of the upper and lower limbs for everyday activities were measured with the Overall Neuropathy Limitation Scale (ONLS), whereas those in disease severity were evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS-v2).

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Unexpected improvements noted in placebo group

Results showed improvements with both PXT3003 and a placebo. According to Pharnext, the unexpected improvements in the placebo group complicate data interpretation, particularly those of the ONLS scale, confirming prior reports supporting the use of this measure in long-term evaluations, but not in shorter term assessments in a clinical trial. Also, the findings failed to reproduce the improvements seen in the prior Phase 3 PLEO-CMT study (NCT02579759).

The data also showed clinical stabilization in treated patients.

“This suggests that PXT3003 might stabilize the condition of patients, which is an important consideration for a disease where progression is generally inevitable,” Pharnext stated in a separate press release. Safety results confirmed the favorable profile seen in previous studies.

“Although the results … are not exactly what we had hoped for, they are nonetheless very promising,” said Brugière.

Though it confirmed the lack of significantly significant ONLS and CMTNS-v2 benefits with treatment, a subsequent analysis looking at patient subgroups suggested a better response in the PXT3003 group, namely in participants with a body mass index, a measure of body fat), below 25 and in those younger than 45.

In addition, according to Pharnext, the random assignment of participants to PXT3003 or a  placebo was not consistent across trial locations, in that patients at some centers received only a placebo, and in others only PXT3003.

The new analysis showed that, when removing centers with fewer than two patients per group, a statistically significant difference exists between the placebo and PXT3003 on CMTNS-v2.

These findings, along with the positive results from past studies that span more than six years, support the potential of PXT3003 for the treatment of CMT1A, according to the company.

“We are now going to make the most of all the data we have accumulated over the last ten years, including our 2 Phase III studies and our 6-year extension study, which tend to demonstrate a beneficial effect on patients,” Brugière said.

The company’s supervisory board and management will decide whether the new analysis is sufficient to request a meeting with the U.S. Food and Drug Administration, or if it’s better to wait for the results from a Phase 3 trial (NCT05092841) led by Pharnext partner Tasly in China. Tasly holds the licensing rights for PXT3003 in China.

“I remind that, today, PXT3003 is the only ray of hope for all CMT1A patients, and that no other drug candidate is currently in an advanced stage. It seems to me, therefore, that efficacy results for a risk-free drug could support an application for regulatory approval and market authorization. This is for us the final stage, which we will move forward with patient community,” Brugière said.