Novel 3-drug combo offers hope for Charcot-Marie-Tooth patients
A novel three-drug cocktail, PXT3003, reduces disability in patients with Charcot-Marie-Tooth Type 1A disease (CMT1A) along with a favourable safety profile, according to the PLEO-CMT study presented at AAN 2019, providing hope for a rare disease which so far has no cure.
CMT1A is a rare chronic, peripheral neuropathy, which affects 1 in 5,000 people, according to Dr Florian Thomas of Hackensack University Medical Center in Hackensack, New Jersey, US. Though rare overall, CMT1A is the most common inherited disorder involving the peripheral nerves.
“To date, no treatment is available to stabilize or reverse the disease,” said Thomas. “Patients suffer from distal-dominant muscle atrophy compromising gait and activities of daily living, stocking-glove sensory loss, and overall reduced quality of life.”
PTX3003 is an oral three-drug cocktail comprising baclofen, naltrexone, and sorbitol in fixed doses — combination of which is believed to have synergistic effect on the inhibition of PMP22, a gene that encodes peripheral myelin protein and found to be overexpressed in CMT1A.
The multinational, double-blind, pivotal phase III trial enrolled 323 patients aged 16–65 years with genetically-confirmed CMT1A of mild-to-moderate severity. They were randomized 1:1:1 to placebo, low-dose PXT3003 (comprising 3 mg baclofen, 0.35 mg naltrexone, and 105 mg sorbitol) or high-dose PXT3003 (comprising all three drugs at twice the dose of the low-dose treatment) twice daily for up to 15 months. [AAN 2019, abstract ES.001]
The high-dose group had a clinically meaningful reduction of 0.37 point (95 percent confidence interval [CI], 0.10–0.64) on the Overall Neurology Limitations Scale (ONLS) compared with the placebo group (p=0.008), thus meeting the study’s primary endpoint.
The high-dose group also trended towards improvement on the ONLS compared with a baseline score of -0.20 point (p=0.098).
Furthermore, participants treated with high-dose PXT3003 improved by 0.47 seconds in the 10-metre Walk Test compared with the placebo group (p=0.016).
Treatment-emergent adverse events (TEAEs) leading to discontinuation occurred at a low rate and were similar among the three groups (5.5 percent, 5.3 percent, and 5.6 percent for low-dose, high-dose PXT3003, and placebo arms, respectively). The overall safety profile was similar to that observed in phase II, Thomas reported.
“PXT3003 is the first treatment for CMT1A demonstrated to be effective, safe, and well tolerated,” said Thomas.