Oral-ATO as the new standard of care in APL The drug oral-ATO – which stands for oral formulation of arsenic trioxide – has already been shown in local and regional trials to be an effective cure for acute promyelocytic leukaemia (APL). Recently, it obtained orphan drug designation from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), which recognise that the drug is a promising treatment for this rare disease. ‘Oral-ATO is a game-changer for APL patients because it is life-saving, cost-effective and preserves patients’ quality-of-life, and we take great pride in seeing our research translated into practice in Hong Kong and elsewhere. Our aim is to make APL a curable disease for patients around the world,’ said Professor Harinder Gill, Clinical Associate Professor in the Department of Medicine, SClinMed, who is now the lead investigator on the drug. A Long Road from Lab Bench to Patient Care But the journey to this stage has been long and involved multiple generations of scholars carrying the research forward. It all started back in 1997 when Professor Kwong Yok-lam, Chair of Haematology/ Oncology and Bone Marrow Transplantation, sought to make something old – and highly toxic – new again. The ‘something’ was arsenic, a substance often associated with murder in history. Arsenic trioxide was used in medicine for centuries but fell out of favour over its toxicity. However, in 1997 Professor Kwong read an article about the successful use of intravenous arsenic trioxide in treating leukaemia patients in Shanghai. He brought the article to his supervisor Professor David Todd, who recalled the successful use of oral arsenic trioxide in the early 1950s in Hong Kong. Professor Kwong confirmed the case. However, it was difficult to import medicine from the mainland at the time, and inspired by the 1950s case, he decided to develop an oral rather than intravenous formulation of arsenic trioxide. He teamed up with Professor Cyrus Kumana (now Emeritus), who was then chief in the Division of Clinical Pharmacology, to work on creating the oral formulation. Over the next three years, the team overcame challenges such as sourcing pharmaceutical grade arsenic trioxide powder, controlling its solubility and securing ethics approval, until they had a preparation that they felt could be safe and effective for patients. An unusual clinical trial was then organised. ‘We had no recourse to prior testing in normal volunteers because they would be unlikely to take arsenic. And there was no recourse to comparison with a placebo or dummy treatment. Instead, we treated patients with relapsed APL who were very, very sick,’ said Professor Kumana. Outstanding Clinical Results The results, which were followed up in a 15-year prospective study, found that among more than 80 relapsed patients treated with oral-ATO, there was a molecular remission rate of 100% and a five-year overall survival rate of 80%. Importantly, they were also able to show that oral-ATO had a bioavailability comparable with intravenous ATO. The team then tested oral-ATO as a maintenance treatment of APL patients in complete remission. Here ‘We had no recourse to prior testing in normal volunteers because they would be unlikely to take arsenic.’ Emeritus Professor Cyrus Kumana 23 HKUMed News Summer 2025
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