On February 10, 2025, the Faculty of Medicine at the University of Hong Kong announced that their research team successfully developed arsenic trioxide (commonly known as arsenic) into an oral medication (also called "medicinal oral arsenic" or "ARSENOL?") for the treatment of Acute Promyelocytic Leukemia (APL). Following treatment, the overall survival rate of patients exceeded 97%. Notably, this drug is the first cancer prescription drug independently developed in Hong Kong and is the first to obtain patent authorization in the United States, Europe, and Japan. It has received clinical research qualification certification from the US FDA and the European EMA, and the Guangdong Provincial Drug Administration has approved its clinical application in the Greater Bay Area, bringing hope to more patients.
When it comes to arsenic trioxide, many might find it both unfamiliar and familiar. The reason it's unfamiliar is that most people have never seen arsenic trioxide in person, nor do they know what it looks like. Arsenic trioxide is a refined product of arsenolite sublimated into arsenic trioxide. It is white, odorless, and tasteless, with the ability to treat ulcers, kill insects, remove phlegm, and treat malaria. It is the most commercially valuable arsenic compound. An impure form of arsenic trioxide is also known by another name we are familiar with, "HeDingHong (鶴頂紅)."
In fact, using arsenic trioxide to treat leukemia is not a discovery of recent years. As early as the 1970s, there was a folk remedy in Lindi County, Heilongjiang Province, that claimed to treat cancer. This remedy actually consisted of three highly toxic substances (mercury, arsenic trioxide, and toad venom). Inspired by this folk remedy, pharmacist Han Taiyun from Harbin Medical University developed the "Cancer Ling No. 1" injection in March 1971, also known as 713 injection, whose main components were arsenic trioxide and mercuric chloride. According to the information from the National Intellectual Property Administration, Harbin Medical University applied for a national patent for "Cancer Ling No. 1" injection in 1995. In 1999, the NMPA of China approved arsenic trioxide injection as a Class II new drug. A year later, the US FDA approved arsenic trioxide injection for the treatment of APL, and the product was also approved for sale in Europe. However, these products remained in the injection phase, and how to provide oral treatment for middle- and low-risk APL patients remained a significant challenge for researchers.
APL is a special type of Acute Myeloid Leukemia (AML) and is classified by the FAB cooperative group as M3 type of acute myeloid leukemia. Its pathogenesis involves the blockage of differentiation of early promyelocytes in the bone marrow, leading to the accumulation of malignant clones in the bone marrow and other hematopoietic tissues, suppressing normal hematopoietic function. Clinically, it manifests as anemia, bleeding, infection, as well as liver, spleen, and lymph node enlargement. According to the "China Acute Promyelocytic Leukemia Diagnosis and Treatment Guidelines (2018 Edition)," APL is common in young and middle-aged people, with an average onset age of 44 years. APL accounts for 10% to 15% of all AML cases, with an incidence rate of about 0.23/100,000. APL used to be one of the deadliest subtypes of leukemia, but with the use of retinoic acid and arsenic agents, APL has become a leukemia that can be cured without hematopoietic stem cell transplantation. As a result, there is a saying in the hematology community: "If you unfortunately get leukemia, it’s best if it’s M3 type."
Currently, the first-line treatment for all APL patients, whether low-risk, intermediate-risk, or high-risk, is all-trans retinoic acid (ATRA) combined with arsenic agents. However, the specific details vary slightly. For low and intermediate-risk patients, the treatment process is as follows: induction therapy with ATRA combined with arsenic trioxide or Compound Huangdai tablets until complete remission (about 1 month), followed by consolidation therapy with ATRA for 2 weeks, with a 2-week break for each cycle, for a total of 7 cycles. For high-risk APL patients, chemotherapy induction, chemotherapy consolidation, and alternating ATRA/arsenic maintenance therapy are added to the ATRA+arsenic treatment regimen. All the arsenic trioxide mentioned above is administered via intravenous infusion. As a result, traditional APL treatment regimens are quite complicated and require professional training for medical staff to administer.
In February 2025, at a press conference held by the University of Hong Kong’s Faculty of Medicine, patient Ms. Huang from Hong Kong mentioned, "The taste of the oral arsenic medication is like seawater. I just need to open it and drink it, and I can go back to work as usual." Compared to intravenous injections, the oral arsenic solution developed by the University of Hong Kong is considered a "treatment breakthrough." It successfully shortened the patient's hospitalization period from approximately 100 days to as little as 14 days, allowing patients to return to normal life more quickly. This oral treatment regimen consists of three active ingredients: arsenic trioxide, all-trans retinoic acid (ATRA), and ascorbic acid (Vitamin C), which together form the "AAA" regimen. The treatment is adjusted according to the patient's risk level. Clinical practice has shown that the bioavailability of oral administration is almost the same as intravenous injection. In fact, the University of Hong Kong had begun extensive research on medicinal oral arsenic trioxide for treating APL more than 20 years ago. From a 15-year prospective follow-up study previously published, it is known that more than 400 relapsed APL patients have been treated with oral arsenic trioxide, with molecular remission rates and 5-year overall survival rates reaching 100% and 80%, respectively.
In December 2023, the University of Hong Kong reported the results of an ongoing multicenter trial on oral arsenic trioxide for APL at the 65th American Society of Hematology (ASH) meeting, publishing the results in the ASH journal "Blood Advances" [1]. According to the report, the trial adjusted the dosage of arsenic trioxide, ATRA, and ascorbic acid based on the patient's age and risk level (i.e., white blood cell count). The results showed that from January 2018 to July 2023, 5 adolescent patients aged 3-15 and 116 adult patients received the oral AAA regimen. Of these, 90 were low and intermediate-risk patients, and 31 were high-risk patients. Among them, 7 had already died before receiving the AAA regimen induction therapy, while the remaining 114 patients achieved the first complete remission (CR1) after induction treatment with the oral AAA regimen. After subsequent maintenance therapy, the 3-year overall survival rate (OS) and relapse-free survival rate (RFS) were 97.9% and 99.1%, respectively. The most common side effects were elevated transaminases and headaches, with incidences of 47.3% and 28%, respectively. This shows that the AAA treatment regimen is safe and effective for APL patients of different ages and risk levels, minimizing the need for chemotherapy.
Currently, this drug has received rare disease drug qualification from the US FDA and the European EMA, and it is hoped that in the near future, this drug can benefit APL patients worldwide, bringing a major change to the treatment regimen and significantly improving the quality of life for patients!
[1]. Harinder Gill, Rita Yim, Lynn Chin, Paul Lee, Vivian Li, Lester Au, Garret Man Kit Leung, Ka Leung Daniel Cheuk, Shau-Yin Ha, Chi Kong Li, Melissa Ooi, Wee-Joo Chng, Patrick Chu, Cyrus Kumana, Yok Lam Kwong; An Entirely Oral Regimen of Oral-Arsenic Trioxide/All-Trans Retinoic Acid/Ascorbic Acid in Newly-Diagnosed Acute Promyelocytic Leukaemia (APL): Updated Results of an Ongoing Multicentre Trial. Blood 2023; 142 (Supplement 1): 157. doi: https://doi.org/10.1182/blood-2023-179644
|
