The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Kymera Therapeutics’ KT-253 for the treatment of Acute Myeloid Leukemia (AML).
KT-253 is a highly potent and selective degrader that targets MDM2, the crucial regulator of the most common tumor suppressor, p53. p53 remains intact (wild type) in close to 50% of cancers, meaning that it retains its ability to modulate cancer cell growth.
While small molecule inhibitors have been developed to stabilize and upregulate p53 expression, they have been found to induce a feedback loop that increases MDM2 protein levels, which can repress p53 and limit their efficacy.
In preclinical studies, KT-253 has shown the ability to overcome the MDM2 feedback loop and rapidly induce cancer cell death, even with brief exposures. Given MDM2 overexpression and amplification is implicated in AML, KT-253 is being explored in this cancer, as well as other liquid and solid tumors.
“This orphan drug designation reinforces the potential of KT-253 to advance the treatment of AML by targeting MDM2, a protein that has been challenging to effectively drug with conventional medicines,” said Nello Mainolfi, founder, president and CEO, Kymera Therapeutics. “We have a significant opportunity to deliver an important new medicine that acts on this common cancer mechanism, and we look forward to rapidly advancing KT-253 in AML and exploring its potential in other hematological and solid tumors.”
The Phase 1 study initiated in March 2023 will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and clinical activity of KT-253 in patients with relapsed or refractory high grade myeloid malignancies, including AML, acute lymphocytic leukemia (ALL), lymphoma and solid tumors.
Patients in the KT-253 Phase 1a dose escalation study will receive IV doses of KT-253 administered once every 3 weeks. The open-label study is intended to identify the recommended Phase 2 dose for KT-253, and is comprised of two arms, with ascending doses of KT-253 in each arm. The first arm will consist of patients with lymphomas and advanced solid tumors and the second arm will consist of patients with high grade myeloid malignancies and ALL.
The FDA’s Orphan Drug Designation program provides orphan status to drugs defined as those intended for the treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity upon FDA approval.
