Convergence Pharmaceuticals' Novel Sodium Channel Blocker CNV1014802 Shows Excellent Efficacy and Safety in Ground-breaking Phase II Trigeminal Neuralgia Study

CAMBRIDGE, England, June 16, 2014 /PRNewswire/ --

Convergence Pharmaceuticals  

("Convergence" or "the Company")

Highlights of the data: 

• CNV1014802 was associated with a consistent reduction of pain severity and number of paroxysms in all primary and secondary outcomes 
• 2.3 unit reduction in numeric rating scale (NRS) of pain intensity compared to placebo  
• 55% decrease in pain severity vs 18% for placebo 
• 60% average reduction in number of paroxysms compared to 12% in the placebo group 

Convergence Pharmaceuticals Holdings Limited ("Convergence"), the company focused on the development of novel and high value analgesic medicines for the treatment of chronic pain via a genetically defined approach, today 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: http://www.ncbi.nlm.nih.gov/pubmed/24267010?dopt=Abstract

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."

About Convergence Pharmaceuticals 

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. The Company, led by CEO Clive Dix, was formed in October 2010 following the acquisition of certain neuroscience clinical assets from GlaxoSmithKline ("GSK"). The Company has a pipeline of differentiated clinical-stage compounds targeting the points of convergence in chronic pain signalling through modulation of specific ion-channels.

Convergence Pharmaceuticals is well funded and raised US$35.4 million in Series A financing from a syndicate of leading European and US financial institutions. For more information please go to the Company's website at http://www.convergencepharma.com.

About Trigeminal Neuralgia (TGN) 

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.  

The majority of people affected are over 50 years of age, however many cases have been reported in young adults. TGN is more prevalent in women than men, and for most sufferers, the condition is progressive and worsens over time.

About chronic pain  

Currently, more than 1.5 billion people worldwide suffer from chronic pain of varying degrees. Among all types of chronic pain, neuropathic pain stands out with approximately 3-4.5% of the global population affected, with incidence rate increasing in line with increased age of the population. With the unmet clinical need so high, the demand for better pain management therapies, addressing acute and chronic pain, is on the rise. The global pain management market is set to reach US$60 Billion by 2015^[1].

The Pain therapeutic area encompasses any disease where pain is a major symptom. The unmet medical need for patients in pain is enormous, with the greatest need being for a more effective therapy that is well tolerated and safe over a long period of time. Within the pain marketplace, current pain treatments are unsatisfactory; overall efficacy is poor (typically 1-2 point reductions on a 10 point scale) and satisfactory to less than 50% of patients. Whilst treatments, such as opioids and non-steroidal anti-inflammatory drugs, are available on the market, many patients obtain little or no relief from these existing analgesics and often such drugs are associated with adverse events, side effects and addiction concerns.

References:  

1. Global Industry Analysts Inc. 2010, "Pain Management: A Global Strategic Business Report".

http://www.strategyr.com/Pain_Management_Market_Report.asp

For more information about Convergence Pharmaceuticals, please contact:
Convergence Pharmaceuticals
Dr Clive Dix, Chief Executive Officer
Brenda Reynolds, Chief Operating  Officer
Dr Simon Tate, Chief Scientific Officer
T: +44-(0)1223-755-501
E: info@convergencepharma.com

Consilium Strategic Communications
Mary-Jane Elliott/ Amber Bielecka/ Matthew Neal/ Lindsey Neville
T: +44-(0)20-3709-5700
E: convergence@consilium-comms.com