VALENCIA, SPAIN – The prospect of a new and effective oral medication for trigeminal neuralgia with much better patient tolerability than what’s currently available caused a stir at the International Headache Congress.
In a double-blind, randomized, 7-week, phase II, proof-of-concept study of 31 patients with frequent daily paroxysmic episodes of trigeminal neuralgia, the investigational agent known for now as CNV1014802 had a treatment failure rate that was half the rate seen in placebo-treated controls, Dr. Joanna Zakrzewska reported at the meeting, which was sponsored by the International Headache Society and the American Headache Society.
Dr. Joanna Zakrzewska
“We saw remarkably few adverse events. Drug-related adverse events were confined to a couple of episodes of mild dizziness/headache. There was no cognitive impairment. With the good tolerability, we think these results are encouraging enough to plan further randomized controlled trials,” said Dr. Zakrzewska of University College London.
Trigeminal neuralgia is an uncommon but severe form of unilateral episodic facial pain typically occurring in sudden, stabbing bursts lasting less than 2 minutes. The current first-line treatments – carbamazepine and other anticonvulsants – are quite effective, but often poorly tolerated, have significant drug-drug interactions, and require lengthy titration. All of this adds up to a high treatment failure rate.
CNV1014802 is a state-dependent sodium channel blocker that can be started at its target dose and has selectivity for the Nav 1.7 sodium channel.
The proof-of-concept study had an unusual design. All 31 participants were known to be responders to the novel agent because they were among the 70% of patients who responded to the drug during an open-label screening period. They were then randomized double-blind to CNV1014802 at 150 mg three times a day or placebo.
The primary endpoint in the study was treatment failure, defined as at least a 50% increase from baseline in frequency of paroxysms, a 50% worsening of the associated pain severity, and a physician global impression that a patient was “much worse” or “very much worse.” This occurred in one-third of patients on the novel drug and 64% of those on placebo. The time to treatment failure, when it occurred, was significantly longer in the active treatment group as well, according to Dr. Zakrzewska.
The treatment failure rate was 33% in patients with trigeminal neuralgia randomized to oral CNV1014802 and 64% in placebo-treated controls.
Patients in the active treatment arm experienced a mean 60% decrease in their number of pain paroxysms per day through week 7 as recorded in patient diaries, compared with a 13% reduction in placebo-treated controls. The CNV1014802 group also had a mean 55% reduction in pain severity versus an 18% improvement in controls.
The study results met with an enthusiastic audience response. “This is fantastic news for patients with trigeminal neuralgia,” said Dr. Peter J. Goadsby, chair of the British Association for the Study of Headache, who was charged with summing up the IHC Congress highlights.
Dr. Zakrzewska received a research grant from Convergence Pharmaceuticals, which sponsored the study.