Convergence Pharmaceuticals Holdings Limited (Convergence), an independent biotechnology company, announces positive data from the phase II clinical trial of novel sodium channel blocker CNV1014802 in patients with trigeminal neuralgia (TGN), a very severe form of facial pain.
CNV1014802 is a novel small molecule state-dependent sodium channel blocker that exhibits potency and selectivity against the Nav1.7 sodium channel. Following an initial 21 day open-label treatment period with CNV1014802 at a dose of 150mg three times a day (tid), patients who showed a successful response in the final week of the period, defined as a 30% or more reduction in numbers of paroxysms, or severity of paroxysms, relative to the run-in period, were then randomised to a 28 day double-blind treatment period with either CNV1014802 150mg tid or placebo. All patients entering the study had to have a pre-specified number of paroxysmal attacks of at least moderate severity. A total of 67 patients were recruited into the study and 69% of those patients completing the open label period were randomised as clear responders into the double-blind phase of the study. The novel design of this study protocol has been published and is available online:
CNV1014802 was well tolerated and the study showed a consistent reduction of pain severity and number of paroxysms in all primary and secondary outcomes. In the primary endpoint of the study there was a treatment failure rate of just 33% for CNV1014802 vs 65% for placebo and a favourable separation from placebo on the Kaplan Meier time to relapse. CNV1014802 showed a 2.3 unit decrease in the NRS scale for pain intensity, 60% reduction in paroxysms vs. 12% in placebo and pain severity dropped by 55% vs. 18% placebo, by the end of the study. There were no serious adverse events related to the drug and the adverse event profile of the drug was similar to placebo in the double blind phase of the study. The full study will be published at the International Association for the Study of Pain (IASP) World Congress of Pain, Buenos Aires in October 2014.
CNV1014802 received orphan-drug designation from the US Food and Drug Administration in July 2013 and Convergence will utilise these data to design a pivotal clinical study to start in early 2015 with a view to commercialising an orphan drug as soon as possible.
This is the first well powered, randomized and placebo controlled clinical trial to demonstrate efficacy of a selective state dependent Nav1.7 inhibitor in a chronic pain indication. This follows years of intensive research and provides huge promise for a better standard of treatment for TGN in the future.
Clive Dix, chief executive officer of Convergence, commented: "We are delighted by the results of this study which we believe will form the cornerstone of the Convergence investment case as we look to progress the Company's portfolio through to commercialisation. Based on these data, we will advance CNV1014802 in to clinical studies with a wider patient population and believe that CNV1014802 will offer tremendous relief to sufferers of TGN and other chronic pain conditions."
Professor Joanna M Zakrzewska, an expert in the field of facial pain, Chief Investigator, University College London Hospitals NHS Foundation (UCLH), commented on the results: "Having worked in the field of TGN for over 20 years and managed hundreds of patients with this severe facial pain it is wonderful news to find that there is potentially a new drug to add to our armoury which not only is effective but is also so well tolerated. This is the first time that we have a drug specifically being trialled in TGN rather than using a previously developed anti-epileptic drug. I am impressed that Convergence decided to use a randomised control trial design rather than just reporting case series, which are subject to enormous bias, to test the efficacy and tolerability of CNV1014802. It has been a pleasure to work with such a dedicated team and to have set up an international network of centres keen to work together to develop a much needed new drug for TGN which could substantially improve the quality of life of these patients."
Trigeminal Neuralgia (TGN) is a very severe form of facial pain that is experienced in short bursts or attacks. The IASP defines TGN as sudden, severe, brief, stabbing, recurrent episodes of pain usually on one side of the face and can be provoked by light touch. The pain follows one or more branches of the trigeminal nerve which provides nerve sensation from the mouth, face and the front of the scalp. The severity of pain and its unpredictability results in profound effects on the quality of life of these patients resulting in significant depression which has led to suicides.
TGN currently affects approximately 50,000 people in the USA alone. The condition is commonly misdiagnosed and, to date, there is no guaranteed cure for the condition. Current therapies are centred on sodium channel blockers such as carbamazepine or oxcarbazepine as first-line treatments. However, these agents although providing relief, all result in significant side effects especially cognitive ones which further impact on quality of life, and require lengthy dose escalation, resulting in sub-optimal efficacy. There is also a recognised potential for drug interactions which can be a significant problem in a population that is often on other medications.
Convergence Pharmaceuticals is an independent biotechnology company focused on the development of novel analgesics with potentially commercially attractive efficacy, responder-rate and side effect profiles.