by Researchers from the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, in collaboration with other organizations, have discovered a next-generation BTK degrader that could be effective in treating chronic lymphocytic leukemia (CLL) and related blood cancers. The findings, published in the journal Science, present a potential therapeutic option for CLL patients who have developed drug resistance or are unresponsive to frontline treatments.
The newly identified compound, known as NX-2127, not only inhibits the cellular molecule BTK but also goes a step further by targeting and destroying it. This innovative approach falls under a new drug class called BTK degraders, which shows promise in tackling treatment resistance in CLL.
CLL is an incurable cancer that affects the blood and bone marrow and is responsible for approximately one-fourth of new leukemia cases in the US each year. It primarily affects older adults, with the average age at diagnosis being 70.
Patients diagnosed with CLL are typically prescribed targeted drugs known as BTK inhibitors, which can shrink tumors, alleviate symptoms, and extend lifespans. However, some patients develop drug resistance, limiting their treatment options.
The currently approved BTK inhibitors, such as ibrutinib, work by inactivating the BTK enzyme responsible for keeping B cells alive in leukemia. While these drugs modulate BTK activity, they do not destroy their targets, unlike the new BTK degraders.
In a recent study, Dr. Justin Taylor, a Sylvester hematologist-researcher, and his team evaluated the efficacy of NX-2127 in laboratory studies and a Phase I clinical trial involving patients with drug-resistant tumors or those unresponsive to existing therapies.
Developed by Nurix Therapeutics, NX-2127 consists of two modules—one that binds to the BTK molecule and another that degrades and eliminates it, hence its classification as a BTK degrader.
The researchers found that NX-2127 effectively destroyed its cellular targets both in vitro and in patient cells. Notably, the compound was able to destroy BTK in tumors that had become resistant to currently available BTK inhibitors. In the Phase I clinical trial, 11 out of 14 CLL patients experienced tumor shrinkage when treated with NX-2127, indicating its potential therapeutic benefit.
Furthermore, a remarkable response to the BTK degrader was observed in one patient who had previously developed resistance to other therapies, leaving them with limited treatment options. During the trial, the patient’s symptoms improved, and their quality of life was enhanced to the point where transfusions for anemia were no longer required.
Although the data for this study had a cutoff date of September 2022 for publication in Science, an update was provided in December at the American Society of Hematology meeting. The latest findings revealed that 41% of CLL patients responded positively to NX-2127, with the patient previously mentioned continuing to show a favorable response to the drug.
The results of this study indicate that BTK degraders, such as NX-2127, hold promise in overcoming treatment resistance in CLL and could provide a new treatment option for patients who have exhausted conventional therapies. Further research and clinical trials are needed to fully understand the potential of this novel compound in improving outcomes for CLL patients.
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1. Source: Coherent Market Insights, Public sources, Desk research
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