Oral arsenic trioxide for acute promyelocytic leukaemia – HK’s first prescription medication to go global

Oral arsenic trioxide (ATO) for the treatment of acute promyelocytic leukaemia (APL), developed at the Li Ka Shing Faculty of Medicine at the University of Hong Kong (HKU), is the first-ever prescription medication wholly invented and manufactured in Hong Kong to obtain US, European and Japanese patents, and the first to receive orphan drug designation (ODD) from US FDA and the European Medicines Agency (EMA) as well as an investigational new drug designation (IND) from the US FDA. According to APL Asian Consortium’s (APLAC) data collected over a 21.5-year period, frontline oral or intravenous (IV) ATO significantly decreases early deaths and improves relapse-free survival (RFS) and overall survival (OS) vs ATO-free regimens.

How curable is APL, really?

APL, which arises from PML::RARA fusion, is a rare type of acute myeloid leukaemia (AML). According to clinical trial data, durable remission, which can potentially translate into cure, is observed in >90 percent of newly diagnosed patients. Such results, however, are not reproduced in routine practice. Patients with APL typically present with profound thrombocytopenia and coagulopathy, which, without timely intervention, often lead to death. Furthermore, all-trans retinoic acid (ATRA), a key component of standard induction regimens for APL, is available in only a minority of treatment centres even in countries with advanced medical systems. In resource-constrained regions, it is often impossible to implement standard treatment algorithms. These factors reduce the survival of patients with APL, which otherwise ought to be highly curable. [Blood Adv 2025;9:862-876]

Why oral ATO is better

ATO is a crucial component in the treatment of APL. Used initially in relapsed disease, it is now also indicated in newly diagnosed patients. Outside of Hong Kong, where an oral formulation has been available for over two decades, ATO is only available as a costly IV preparation. According to data from Hong Kong, where oral ATO has been used in both relapsed and newly diagnosed patients, outcomes with the oral formulation are comparable with those with IV ATO. Advantages of oral ATO include improved cardiac safety, significant cost savings because of its outpatient administration and low unit cost, and possibility of maintenance use, which is not feasible with the IV formulation. [Blood Adv 2025;9:862-876]

21.5 years’ worth of data

APLAC was established in 2020 to determine the unmet needs and improve the management of APL in Asia. As ATO is not currently available for the treatment of newly diagnosed APL in a number of Asian countries, APLAC was able to compare contemporaneous cohorts of patients with APL managed with or without ATO.

The retrospective multicentre study analyzed data collected between January 2001 and July 2022 from adult patients with newly diagnosed APL treated across six Asian academic centres: two in Malaysia and one in Hong Kong, Singapore, Taiwan, and Thailand each. [Blood Adv 2025;9:862-876]

During the 21.5-year study period, 647 consecutive patients (median age, 45.5 years; male, 50.1 percent; high-risk disease, 31.5 percent) with newly diagnosed APL were treated with one of three regimens. The first regimen was ATRA/chemotherapy (n=436), comprising induction (ATRA + idarubicin), consolidation (ATRA + mitoxantrone + idarubicin + cytarabine), and two different maintenance strategies (one not containing ATO [non-ATO; ATRA + methotrexate + 6-mercaptopurine] and the other containing oral ATO [ATRA + oral ATO + ascorbic acid [AAA]). The second regimen was ATRA/IV ATO (n=61), comprising induction (ATRA + idarubicin/IV ATO), consolidation (ATRA + IV ATO), and maintenance (ATRA + methotrexate + 6-mercaptopurine). The third regimen was oral AAA (n=150), comprising induction (AAA ± hydroxyurea/daunorubicin), consolidation (AAA + daunorubicin + cytarabine), and maintenance (AAA).

The ATRA/chemotherapy group had a significantly higher rate of early deaths within 60 days (8.3 vs 3.3 and 3.3 percent; p=0.05), inferior 60-day survival (91.7 vs 98.4 and 96 percent; p<0.001), inferior 5-year RFS (76.9 vs 92.8 and 97.8 percent; p<0.001), and inferior 5-year OS (84.6 vs 91.4 and 92.3 percent; p=0.03) vs ATO-containing groups (ATRA/IV ATO and oral AAA). Of note, ATO maintenance partly mitigated the inferior 5-year RFS in the absence of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV ATO vs oral AAA, 71.1 vs 87.9 vs 92.8 vs 97.8 percent; p<0.001).

Due to uncertainties regarding ATO’s relative benefits in low-/intermediate- and high-risk APL cases, the investigators examined the effect of ATO use across different patient categories. For low-/intermediate-risk disease, the ATRA/chemotherapy group had a significantly inferior 5-year RFS vs the ATRA/IV ATO and oral AAA groups (78.6 vs 95.7 and 95.7 percent; p<0.001). For high-risk disease, induction with ATRA/chemotherapy was associated with a significantly inferior 60-day survival vs the ATRA/IV ATO and oral AAA groups (84.4 vs 95.3 and 95.3 percent; p=0.03). Notably, when ATO (IV or oral) was included in the treatment algorithm (induction or consolidation or maintenance), low-/intermediate-risk and high-risk patients had comparable survival outcomes.

“The favourable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS,” summarized the investigators.

Going global

Oral ATO has been available in Hong Kong for over two decades. It is also approved by the Guangdong Provincial Medical Products Administration (GDMPA) for clinical use in the Greater Bay Area via the HKU-Shenzhen Hospital and is available for research and clinical use in APL patients in Singapore, Malaysia, and Taiwan.

Oral ATO has recently received ODD from US FDA and EMA and obtained an IND from the US FDA, making it the first prescription anticancer drug developed in Hong Kong to secure key US FDA and EMA designations. Clinical studies in North America and Europe are set to commence later this year.

In addition, the UK AML Research Network and the University of Cardiff, UK, have recently obtained funding from Blood Cancer UK to investigate the use of oral ATO in frontline management of APL in a nationwide phase III study.

Towards curing APL worldwide

“We take great pride in seeing our research translated into practice in Hong Kong and around the world,” said lead investigator, Dr Harinder Gill, of the Department of Medicine, School of Clinical Medicine, HKU. “The development of oral ATO is a game-changer for APL patients. It offers a convenient and effective treatment option that can significantly improve their quality of life. We are proud to play a pioneering role in bringing this innovation to the world and are committed to ensuring that all APL patients have access to this life-saving and cost-effective therapy. We aim to make APL a curable disease for patients around the world.”