FDA grants Breakthrough Therapy Designation to TERN‑701 in chronic‑phase Ph+ CML after ≥2 TKIs, supporting accelerated development of the investigational allosteric BCR::ABL1 inhibitor.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Terns Pharmaceuticals secured a major regulatory milestone after the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to TERN‑701 for adult patients with Philadelphia chromosome‑positive chronic myeloid leukemia (Ph+ CML) in chronic phase without the T315I mutation who previously received two or more tyrosine kinase inhibitors (TKIs).
The designation strengthens the development path for TERN‑701, an investigational oral allosteric BCR::ABL1 inhibitor currently under evaluation in the ongoing Phase 1/2 CARDINAL study (NCT06163430). The FDA awards BTD to investigational therapies that show preliminary clinical evidence of substantial improvement over available treatments in serious diseases with unmet medical need.
Chronic myeloid leukemia remains largely driven by the BCR::ABL1 fusion protein, a constitutively active tyrosine kinase that promotes uncontrolled leukemic cell growth. While TKIs have transformed long‑term outcomes in CML, resistance, intolerance, and suboptimal molecular responses continue to limit treatment durability for many patients after multiple prior therapies.
TERN‑701 targets BCR::ABL1 through an allosteric mechanism distinct from ATP‑competitive TKIs, an approach that may help overcome resistance pathways while potentially improving tolerability and enabling deeper molecular responses.
The FDA’s decision was based on emerging data from the CARDINAL trial, which enrolled patients with CML previously treated with at least one prior TKI who experienced treatment failure, intolerance, or inadequate response. Investigators reported encouraging rates of major molecular response (MMR) and deep molecular response (DMR) by week 24, including among heavily pretreated patients and those previously exposed to another allosteric TKI.
Safety findings also supported the designation, with most treatment‑emergent adverse events reported as low grade and severe events or discontinuations occurring infrequently.
Scott Harris, chief development and operations officer at Terns, said the designation highlights the potential for TERN‑701 to improve efficacy, safety, and tolerability compared with currently available therapies, pointing to the rapid and deep molecular responses observed to date.
Chief executive officer Amy Burroughs added that the designation, together with Merck’s planned acquisition of Terns, could accelerate advancement of TERN‑701 into pivotal‑stage development and potentially speed access for patients.
References
About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.