Medical Innovation Exchange

Pharnext blames ‘unexpected’ placebo results for lead neurological drug’s phase 3 failure

Less than a year after Pharnext dropped its Alzheimer’s program over cost concerns, the French biotech has seen its lead program fail a phase 3 trial in a rare neurological disease.

The company is developing PXT3003 in Charcot-Marie-Tooth disease type 1A, an inherited genetic disorder that affects the peripheral nerves, resulting in muscle weakness and potentially sensory loss.

The 387-patient trial did not show that the drug was able to improve functional motor disability as measured by the Overall Neuropathy Limitation Scale (ONLS), the company revealed in a Dec. 11 release. Pharnext blamed an “unexpected” improvement in the disease among the placebo cohort, which it said “complicates the interpretation of the results.”

“It also confirms what the medical literature as a whole has been saying for many years, namely that ONLS is undoubtedly a relevant endpoint over the long term, but not over such a short period of time as a clinical study,” the company claimed in the release.

Trying to see the bright side, the biotech said there had been “no deterioration” of the condition among the patients who received the drug. “This suggests that PXT3003 might stabilize the condition of patients, which is an important consideration for a disease where progression is generally inevitable,” it concluded.

PXT3003 is a combination of the approved meds baclofen, naltrexone and sorbitol. The oral drug is designed to downregulate the overexpression of the PMP22 protein in order to improve neuronal signaling in dysfunctional peripheral nerves.

Pharnext hopes incoming data from a phase 3 trial run by its Chinese partner Tasly will offer some better news. In the meantime, the company “plans to continue analyzing the data, particularly in collaboration with potential partners for licensing or acquisition of PXT3003.”

“Although the results we are sharing today are not exactly what we had hoped for, they are nonetheless very promising,” Pharnext’s Manager Hugo Brugière said in the release. “We are now going to make the most of all the data we have accumulated over the last 10 years, including our two phase 3 studies and our 6-year extension study, which tend to demonstrate a beneficial effect on patients.”

“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,” Brugière added. “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”.

Investors didn’t appear to see much cause for optimism, sending the company’s share price plunging 68% on Monday morning. However, with the company’s stock already sitting at below one euro cent, the difference was negligible in practicable terms.

Pharnext’s stock crashed back in February, when the biotech walked away from its potential Alzheimer’s asset, dubbed PXT864, arguing that the encouraging data produced to date weren’t enough to lead to commercialization in the “short or medium term.”  Instead, Brugière said at the time that the company would search for a partner to take the clinical baton. 

It left Pharnext even more reliant on PXT3003. The company said in October that it had received potential international licensing offers worth over 250 million euros for the drug, although it remains to be seen whether these as-yet-undisclosed deals will be impacted by today’s results.

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