The Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee recently voted on 2 investigational therapies being developed by Daiichi Sankyo: pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT), and quizartinib for the treatment of adults with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).
When asked whether the benefits of each of these investigational treatments outweighs the risks in their respective patient populations, the panel voted in favor of pexidartinib (12 yes; 3 no) and against quizartinib (3 yes; 8 no).
In meeting documents, the FDA panel noted several issues regarding the credibility of the overall survival data (primary endpoint) in the phase 3 QuANTUM-R study which evaluated quizartinib, an oral selective type II FLT3 inhibitor, vs chemotherapy in adult patients with FLT3-ITD AML that was refractory or that relapsed within 6 months of first remission. In addition to the efficacy data, the panel raised safety concerns over the potential for cardiac toxicity with quizartinib, adding that “the evidence available underscores the serious risk of fatal and life-threatening events with quizartinib.”
Commenting on the panel vote, Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo said, “Patients with relapsed/refractory FLT3-ITD AML are facing a very aggressive disease with poor prognosis, and we continue to believe that quizartinib could offer an important additional treatment option that specifically targets FLT3-ITD, a driver mutation in AML.”
As for pexidartinib, a first-in-class, oral tyrosine kinase inhibitor of the colony stimulating factor 1 receptor, the panel reviewed data from the phase 3 ENLIVEN study which included patients with symptomatic advanced TGCT for whom surgical removal of the tumor would be associated with potentially worsening functional limitations or severe morbidity. Results from the trial showed an overall response rate (ORR; primary endpoint) for the intention-to-treat population of 39.3% in the pexidartinib arm vs 0% for placebo (P<.0001).
In meeting documents, the panel did note that “interpreting the clinical meaningfulness of the observed ORR in the context of a disease setting characterized by an often progressive and debilitating but slow growing and benign tumor poses some challenges in evaluating the durability of tumor responses in the ENLIVEN trial.”
In addition, concerns over potential liver toxicity with pexidartinib, prompted the committee to propose labeling recommendations including: a Boxed Warning regarding the risk of hepatotoxicity, inclusion of information on hepatotoxicity in the Warnings and Precautions section, liver test monitoring recommendations, and a Risk Evaluation and Mitigation Strategy (REMS) program.
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. The New Drug Applications for both drugs are currently under Priority Review with a Prescription Drug User Fee Act (PDUFA) date of August 3, 2019 for pexidartinib and August 25, 2019 for quizartinib.
Quizartinib is also being investigated in a phase 3 trial for use in newly-diagnosed FLT3-ITD AML.
For more information visit FDA.gov.