PXT3003 Designated Promising Innovative Medicine in UK for CMT1A Treatment

The U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted promising innovative medicine (PIM) designation to PXT3003 for the treatment of people with Charcot-Marie-Tooth type 1A (CMT1A) aged 16 and older.

PIM designation indicates that the MHRA considers PXT3003, an experimental oral therapy developed by Pharnext, likely to offer major therapeutic advantages for CMT1A patients and also a promising candidate for the U.K.’s early access to medicines scheme (EAMS).

EAMS seeks to help people with serious or life-threatening conditions gain access to promising therapy candidates for disorders with no or few available medical treatments.

“We are delighted by the MHRA’s decision to award the PIM designation to PXT3003 as it further validates the potential of our lead [therapy] candidate as an innovative treatment approach to address the high unmet medical need in patients with CMT1A,” Daniel Cohen, MD, PhD, Pharnext’s co-founder and CEO, said in a press release.

CMT1A, the most common type of CMT disease, is caused by abnormally high levels of the PMP22 protein, which disrupt the structure and function of the protective myelin sheath around nerve fibers.

PXT3003, an oral solution given twice a day, combines three approved treatments that act on the nervous system — the muscle relaxant baclofen, the opiate and alcohol addiction therapy naltrexone, and the laxative sorbitol. Each therapy has been predicted not only to lower PMP22 levels, but also to play a role in myelin sheath formation and nerve fibers’ integrity.

In a rat model of CMT1A, PXT3003 lowered the levels of PMP22 and made peripheral nerve fibers larger, improving motor function.

Combined two-year data from the pivotal Phase 3 PLEO-CMT clinical trial (NCT02579759) and its open-label extension study, called PLEO-CMT-FU (NCT03023540), showed that PXT3003 was safe and effectively halted disease progression in CMT1A patients.

PLEO-CMT involved 323 CMT1A patients, ages 16 to 65, who were randomly assigned to receive twice daily either a low or high dose of PXT3003, or a placebo, for 15 months. After completing the trial, 187 participants decided to enter the extension study, in which all received PXT3003 for nine months.

Pharnext plans to continue patient dosing in the extension study until PXT3003 is commercially available, and detailed long-term safety and efficacy data are expected later this year.

“All existing data indicate that PXT3003 is a safe and well tolerated therapy combination,” said Cohen.

Based on missing data caused by an unexpected issue with the high dose of PXT3003 in PLEO-CMT, the U.S. Food and Drug Administration (FDA) requested a second Phase 3 trial of the therapy.

The company plans to use the trial’s data to support a marketing authorization application to the European Medicines Agency (EMA).

“We look forward to continuing our discussions with U.S. and European regulatory authorities to advance the clinical development of PXT3003 and initiate as quickly as possible an additional pivotal Phase 3 trial in the U.S. and Europe,” Cohen said.

Recently, Pharnext raised about 7.7 million euros (about $8.4 million) to help finalize the protocol of the upcoming trial, and fund other regulatory requisites placed by the FDA and EMA for continued PXT3003 development.

PXT3003 received orphan drug status in the U.S. and Europe, as well as fast track designation in the U.S. for the treatment of CMT1A. These designations provide regulatory support and financial benefits to accelerate PXT3003’s clinical development and review, while also ensuring marketing exclusivity for a period of time upon regulatory approval (seven years in the U.S. and 10 years in Europe).

The therapy also was granted priority review for the same indication in China, where Pharnext is pursuing a development and registration path with its Chinese pharmaceutical partner Tasly.