AB Science Announces Four Consecutive Responses in the Treatment of Refractory Acute Myeloid Leukemia
AB Science has reported the results of its phase 1 trial combining AB8939 and venetoclax in patients with refractory or relapsed acute myeloid leukemia. According to the company, the first four treated patients all achieved a response, representing a 100% response rate.
Detailed Patient Responses
The fourth patient treated in the phase 1 study had a very high-risk profile, the company indicates. According to the release, this patient had acute myeloid leukemia with a complex karyotype including monosomy of chromosome 5 and a TP53 gene mutation, and was on the third line of treatment after failing two previous protocols. The patient received AB8939 at a dose of 21.3 mg/m² combined with venetoclax for 14 days and achieved a partial response, AB Science specifies. Among the four patients treated with this combination, one patient is in complete remission, one in near-complete response, and two in partial response. These results were achieved after just one 14-day treatment cycle in patients receiving third or fourth-line treatment, two of whom had previously progressed under venetoclax combined with other chemotherapies, according to the company.
Mechanism of Action of AB8939
According to the company, AB8939 operates through a dual mechanism: destabilizing the microtubules of cancer cells and inhibiting the ALDH1A1 and ALDH2 enzymes, which are crucial for the survival of cancer stem cells. The compound has demonstrated in vitro activity in cytarabine-resistant cell lines, including those with unfavorable genetic mutations MECOM and TP53. AB Science states that the combination with venetoclax is based on the low hematological toxicity of both molecules and their complementary mechanisms of action. Venetoclax inhibits the BCL2 protein, which prevents apoptosis in cancer cells, while AB8939 destabilizes microtubules and targets cancer stem cells. The phase 1 trial has completed its first two steps of determining the maximum tolerated dose, established at 21.3 mg/m² for treatments of 3 and 14 days in monotherapy, the group specifies.
Regulatory Discussions and Market Potential
AB Science has begun discussions with the European Medicines Agency and the U.S. Food and Drug Administration regarding three potential registration study options. According to the release, these options concern the use of AB8939 combined with venetoclax in first-line treatment for elderly patients or those with genetic abnormalities, in second or third line for all patients or those with genetic abnormalities, or AB8939 in monotherapy in the MECOM mutation in second or third line. The company estimates the potential market for treatments in refractory or relapsed acute myeloid leukemia at over 2 billion euros per year. According to the company, intellectual property rights related to AB8939 in this indication are protected until 2036 by a composition of matter patent, with a potential extension until 2041. Two patent applications for specific medical uses could extend this protection until 2044 and 2046 for certain subpopulations, the company specifies. AB8939 has received orphan drug designation for acute myeloid leukemia from the EMA and FDA.
