HKU Bulletin August 2010 (Vol. 11 No. 3)

22 The University of Hong Kong Bulletin 23 August 2010 Left : Intravenous arsenic trioxide used about 15 years ago. Middle: Current oral arsenic trioxide used at Queen Mary Hospital. Right : GMP standard oral arsenic trioxide produced by HKU. Working together with Professor Cyrus Kumana, Emeritus Professor and Chief of the Division of Clinical Pharmacology and Therapeutics, his persistence paid off with an almost 100 per cent cure rate. So far, more than a hundred leukaemia patients in Hong Kong have been treated, the majority of whom have been cured. Professor Kwong places the success rate at 98.2 per cent. Despite its reputation as a deadly poison the team has shown oral arsenic to be a safe and effective compound, far safer than the currently-used alternative, intravenous arsenic, the toxicity of which can cause abnormal heart rhythms and even death. Indeed, oral arsenic is so effective that in Hong Kong it has replaced bone marrow transplantation as the standard treatment of patients suffering acute promyelocytic leukaemia, and is also being used in the treatment of other blood cancers, including lymphomas and myeloma. Professor Kwong explains how he stumbled upon the cure. “It has been used for many hundreds of years in Traditional Chinese Medicine,” he says. “There are many entries in medical texts about arsenic being used. Even western medicine started using it about 200 years ago, and we utilized it at Queen Mary Hospital until the 1950s, when it fell out of favour as alternative drugs were developed. Doctors who have been educated in the last 20 years, or so, may have been completely unaware of its medical uses. “Then, a team in Harbin, in China discovered that intravenous arsenic trioxide was very effective in the treatment of this type of leukaemia.” That set Dr Kwong off on his mission to develop an oral alternative, and he spent many hours ploughing through the archival records at the Hong Kong Medical Museum to determine a safe dosage. After two years of research – without any funding - the team successfully prepared an oral formulation that proved effective in clinical studies. All that remained was to secure the US patent, which took another seven years. The reason? A US team had already developed its own version of the intravenous treatment. However, at a cost of around US$2,000 a day, or US$50,000 a month, the intravenous treatment is beyond the budget of most patients, particularly those in developing countries. “Our treatment is a fraction of the cost, and has virtually no side effects.” Which means that when it becomes widely available it is likely to become the sole treatment for acute promyelocytic leukaemia. The University is now investigating the feasibility of making oral arsenic available on compassionate grounds to patients in developing countries. As it is proven to be safe, and can be conveniently prescribed in an outpatient setting, such a programme would potentially save thousands of lives, particularly in Third World countries. In Hong Kong it is likely to be administered free of charge. Professor Kwong says, “Hong Kong has never invented a drug before, this is the first time and we did it without a grant. I didn’t even apply for a grant, because I didn’t think I would be able to secure one. At the time I was only a young academic with little track record in research. Also, in applying for a grant I would have had to explain my methodology and I didn’t want to risk doing that and losing the chance of securing a patent. “But I want people to know that if you want to be innovative you do not necessarily need huge funding. We have made a contribution to medicine without funding and have come up with a drug that can be taken conveniently and economically.” Arsenic may have a reputation as the wronged wife’s preferred poison but this ancient compound is proving a lifesaver for patients of acute promyelocytic leukaemia. A decade in development the drug is the first, created entirely in Hong Kong, to secure a US patent and is poised to attain global status as a hospital prescription medication making it affordable and accessible to patients. Created by a small team in the Department of Medicine, the ingenious development is based on meticulous and diligent research. Professor Kwong Yok-lam, of the Division of Haematology/Oncology and Bone Marrow Transplantation, says he was inspired to continue the work, despite many setbacks, by his patients. “Perhaps if I had been working in a lab I might have given up,” he explains. “But I carried on for the sake of the patients, they needed a cure and that inspired me.” Professor Kwong Yok-lam FROM KILLING to curing No longer the preserve of homicidal maniacs, the development of oral arsenic as Hong Kong’s first ever patented drug reveals a story of ingenuity, innovation and perseverance. Research