BC1036, a novel, non-opioid, non-narcotic treatment based on theobromine, is currently in late-stage development for the treatment of persistent cough. Persistent cough is defined as a cough lasting for more than two weeks after symptoms that lead to the cough having ceased.
Following consultations with a European regulatory authority, BC1036 will enter a single pivotal Phase III trial in Europe, for the treatment of persistent cough in Q2 2012. BC1036 may be available as a marketed cough treatment in Europe within two years of trial commencement, subject to obtaining marketing authorisation. Theobromine is already available as a marketed treatment for cough in South Korea (AnyCough™). Shown to be safe and effective in a large number of people, it is now the fastest growing product in the Korean cough market.
Theobromine is a bitter alkaloid of the cacao plant, commonly found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola or cola nut. Theobromine inhibits the inappropriate firing of the vagus nerve, which is a key feature of persistent cough. Theobromine’s use as an antitussive agent was explored by evaluating its effect on cough and airway sensory-nerve function in humans.
BC1036’s ability to enter a single Phase III trial in Europe is due to the significant historical safety data available for theobromine and its beneficial effect seen in human use to date, with low side-effects.
Patients suffering from persistent cough are often prescribed narcotic agents with a morphine skeleton, such as the opioid codeine or the NMDA antagonist dextromethorphan, or their various combination preparations. However, their efficacy in the prescription setting is questionable and they have undesirable central nervous and peripheral side effects that often lead to their discontinuation or, in worst case, to misuse and abuse. Theobromine’s peripheral mechanism of action differentiates BC1036 from codeine and other centrally-acting agents and leads to its lower CN side effect.
Cough is a protective, primitive reflex in healthy individuals, however, when cough serves no useful role, it is the most common respiratory complaint for which medical attention is sought. Cough leads patients to use “over the counter” remedies as first-line treatments, where annual sales in the USA exceed $2 billion dollars. Among those which claim to have an effect on cough or underlying conditions are cough-suppressants (mostly dextromethorphan), decongestants (e.g. pseudoephedrine), expectorants (e.g. guaifenisin) and certain anti-histamines (i.e. chlorpheniramine). In the US alone, 40 million households turn to dextromethorphan-containing OTC medicines each year to relieve their cough symptoms. However, a number of Cochrane reviews of randomised controlled trials have concluded these treatments may only be modestly effective in decreasing cough in adults with viral upper-respiratory infections.
In children, however, it has not been found to be effective and, notably, the UK’s MHRA has recently ruled that the risks of codeine-based cough syrups outweigh the benefits for under-18s and their use should be confined to adults.
Persistent cough, defined as a cough that lasts for more than two weeks, can be debilitating, socially distressing, and adversely impair quality of life. More common than heartburn and severe headaches, persistent cough imposes a great burden on the sufferer, their families, and society.
Seek signed a licensing agreement with Pernix Therapeutics Holdings, Inc. in May 2012 for the US marketing rights to BC1036. Under the agreement, Pernix will be responsible for the development and launch of the products in areas of cough, cold, sinus and allergy in North America. SEEK will have the rights to commercialise the products in the rest of the world.
Pernix plans to focus on commercializing and marketing OTC products in the US while SEEK plans to launch products into the prescription as well as OTC markets in Europe. Pernix will pay SEEK upfront payments, milestones and royalties in exchange for the rights to develop and market BC1036 in North America. SEEK will in turn pay royalties to Pernix.