Acute promyelocytic leukemia (APL) is a rapidly fatal disease without timely treatment.¹ A recent breakthrough from the University of Hong Kong’s LKS Faculty of Medicine (HKUMed) is changing the global treatment landscape of APL with the development of an oral formulation of arsenic trioxide (oral-ATO).^2-7 Backed by over 20 years of clinical data, oral-ATO has now received orphan drug designation (ODD) from both the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA).^1,8,9 Led by Dr. Singh, Gill Harinder Harry, Clinical Associate Professor at HKUMed, the team is pioneering a new era in APL treatment, bringing this life-saving innovation from Hong Kong to the global stage.^2,7

The invention and application of oral-ATO represent a landmark achievement for Hong Kong’s medical landscape.² Used locally for over two decades in both relapsed and newly diagnosed APL cases, oral-ATO has demonstrated efficacy comparable to intravenous (IV) formulations while offering significant advantages, including improved cardiac safety, reduced treatment costs, and the convenience of outpatient administration.¹ “We take great pride in seeing our research translated into practice in Hong Kong and around the world,” shared Dr. Gill. Extensive clinical studies have confirmed oral-ATO’s high efficacy and safety profile, with a 5-year relapse-free rate (RFS) exceeding 97% in frontline oral-ATO APL therapy, and a significant reduction in side effects and treatment burden.^1-6 A 15-year prospective follow-up study involving over 73 relapsed APL patients reported a 79.5% 5-year overall survival (OS) rate, achieved without the need for bone marrow transplantation.³ Subsequently, oral-ATO was integrated into maintenance therapy for APL patients in first complete remission, resulting in a 89% five-year relapse-free survival (RFS) rate and a 94% OS rate.5 In frontline treatment for newly diagnosed APL, the regimen achieved 100% leukemia-free survival (LFS) and OS at three years.⁴

Building on these successes, the HKUMed research team has developed a comprehensive treatment strategy incorporating timely intervention, supportive care, and the frontline use of oral-ATO.^4,7 This approach has dramatically reduced early mortality rates associated with APL, which historically may reach up to 35% with conventional therapy.^2,6 Currently, HKUMed researchers are evaluating an entirely oral frontline regimen comprising oral-ATO, all-trans retinoic acid (ATRA), and ascorbic acid (AAA) in a risk-adapted manner.^2,7 “The development of oral-ATO is a game-changer for APL patients. It offers a convenient and effective treatment option that significantly improves quality of life,” emphasized Dr. Gill.

The APL Asian Consortium, led by HKUMed, brings together researchers from Taiwan, Thailand, Singapore, and Malaysia to advance APL research.¹ A retrospective analysis conducted by the group demonstrated the superiority of the frontline ATO regimen over traditional chemotherapy-based regimens.¹ Additionally, the inclusion of oral-ATO maintenance significantly improved 5-year RFS in patients who had not received first-line ATP, with benefits observed across both low/intermediate and high-risk disease groups.¹ Their collaborations with institutions across Singapore and China have yielded impressive 3-year OS and RFS rates of 99.1% and 97.9%, respectively.¹⁰ This entirely oral AAA-based induction, used in a risk-adapted strategy that minimized chemotherapy, proved highly effective and safe in newly-diagnosed APL of all risk categories and age groups.¹⁰

In conclusion, the designations and global expansion of oral-ATO mark a transformative moment for both Hong Kong and the global oncology community.^8,9 Notably, oral-ATO is the first prescription anticancer drug invented and manufactured in Hong Kong to secure major regulatory designations, marking a historic milestone and setting the stage for global clinical trials.^2,8,9 By revolutionizing APL treatment with an accessible, cost-effective, and highly effective oral regimen, HKUMed’s innovation is poised to redefine the standard of care for APL patients worldwide.^1,2,7,10

EXPERT PERSPECTIVE

In an interview with Omnihealth Practice, Dr. Singh, Gill Harinder Harry, the lead investigator of the study, shared his insights on the impact and future of oral-ATO in the treatment of APL.

Question 1: What are the key advantages of oral-ATO over conventional IV-ATO formulations, both from a clinical and patient perspective?

Dr. Gill: Oral-ATO offers a better toxicity profile and reduced hospitalization time over IV treatment. It enhances quality of life, enables lesser disruption to the patients’ lives, and reduces healthcare costs. This advancement could transform the future landscape of APL treatment into a largely outpatient, chemotherapy-free approach.

Question 2: What are the key clinical findings from the studies?

Dr. Gill: In relapsed APL patients, oral-ATO combination as reinduction retains an 80% five-year OS rate without any treatment-related mortality. This eliminates the need for bone marrow transplant which is currently the standard of care despite its 10%-20% treatment mortality risk. In the newly diagnosed cohort, the relapse rate was less than 1%, with an OS of 97% primarily due to advanced age. No patients discontinued treatment due to safety concerns or withdrew for any reason.

Question 3: How do you envision the future of APL care evolving over the next 5 to 10 years, especially with the global adoption of oral-ATO?

Dr. Gill: Oral-ATO has been designated as an investigational new drug (IND) by the FDA, meeting the prerequisites for phase 3 registrational studies in the US and EU. Full global registration is expected by 2027, significantly expanding access and outreach worldwide. While IV-APO is not reimbursed in many areas, oral-APO has a much higher likelihood of receiving reimbursement with the growing evidence from both global and local trials. We are also conducting drug repurposing studies on oral-ATO in other subtypes of AML and autoimmune diseases, as it has implications in suppressing TP53, inflammation, and T lymphocytes.