Vanflyta wins nod in KOR…expanded AML targeted therapy options

After an initial FDA denial in 2019, it joined the market as the first targeted therapy

In competition with Rydapt and Xospata…differentiated as a maintenance therapy

Vanflyta (quizartinib), a new targeted therapy for acute myeloid leukemia (AML), has officially been added to first-line treatment options in South Korea, intensifying market competition.

Until now, Vanflyta has faced significant hurdles, including rejections from global regulatory bodies due to safety concerns. However, it has been reevaluated based on survival benefits, signaling a potential shift in the FLT3 inhibitor market, currently dominated by Rydapt (midostaurin) and Xospata (gilteritinib).

A key factor in this market restructuring is Vanflyta's comprehensive treatment model, which includes maintenance therapy for patients with the high-risk FLT3-ITD mutation.

Strategy for targeting FLT3-ITD has been clarified

According to industry sources on February 11, Daiichi Sankyo Korea announced that Vanflyta (quizartinib) obtained approval in Korea.

AML therapy 'Vanflyta'

With this approval, Vanflyta can now be used in combination with standard cytarabine and anthracycline induction therapy and standard cytarabine consolidation therapy for newly diagnosed adult patients with FLT3-ITD mutation–positive AML. It is also approved as a maintenance monotherapy.

Up to 37% of newly diagnosed AML patients carry the FLT3 mutation, with approximately 80% specifically possessing the FLT3-ITD variant. This mutation is known to drive cancer growth, increase recurrence risk, and shorten overall survival. The five-year survival rate for these patients has been reported at about 20%.

The approval is based on the Phase 3 QuANTUM-First study, which involved 539 treatment-naive FLT3-ITD-positive AML patients.

In this study, the Vanflyta group showed a 22% reduction in mortality risk compared with the placebo group. 

At a median follow-up of 39.2 months, the median overall survival (OS) in the Vanflyta group was 31.9 months, more than double the 15.1 months observed in the placebo group.

In terms of safety, addverse events were similar to those of the placebo group, with common observations including febrile neutropenia, hypokalemia, and pneumonia.

In particular, patients who participated in the study received induction, consolidation, and maintenance for up to 3 years, regardless of whether they unwent allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is a distinct advantage of Vanflyta in the clincial field.

Expected to bring a shift to the market centered around Xospata·Rydapt

The FLT3 inhibitor market has been led by Novartis's first-generation Rydapt and Astellas's second-generation Xospata.

While Rydapt reduced mortality by 23% in the RATIFY study when combined with standard therapy, it lacks strong evidence for maintenance therapy post-transplant and has relatively lower selectivity for FLT3-ITD.

(from left) Novartis 'Rydapt', Astellas 'Xospata'

Xospata was commercialized as the first once-daily oral monotherapy for relapsed or refractory AML, with response rates better than those with Rydapt.

However, Xospata failed to demonstrate sufficient clinical benefit in trials for first-line induction or post-transplant maintenance. Because of this, it is firmly established in the market. analysis suggests that this drug has limitations in obtaining an expanded indication spectrum.

Medical experts are focusing on Vanflyta's inclusion of maintenance therapy. While previous inhibitors lacked clear strategies for consolidation, Vanflyta's effectiveness was demonstrated in extending complete remission (CR) and safety through long-term follow-up of over 5 years.

There have been various hurdles for Vanflyta until it was approved in Korea. This drug was originally developed by Ambit Biosciences, which was acquired by Daiichi Sankyo in 2014.

Vanflyta faced a major roadblock in 2019 when the U.S. FDA denied approval. The FDA cited risks of QT interval prolongation and inadequate cardiac toxicity management plans.

The QT interval is measured from the beginning of the Q wave to the end of the T wave on an electrocardiogram (ECG). It represents the total time required for the heart's ventricles to undergo depolarization and repolarization. Abnormally long or short QT interval is linked to the increased risks of abnormal heart rhythm or occurrence eof sudden death.

In the case of Vanflyta, Daiichi Sankyo addressed these risks by enhancing its Risk Evaluation and Mitigation Strategy (REMS) and safety protocols. However, in 2023, the FDA issued a 3-month extension for an additional safety review.

After that, the FDA approved the drug following the Phase 3 QuANTUM-First study, which demonstrated significant benefits in overall survival (OS) for AML patients. This led to Vanflyta's subsequent approvals in Europe and South Korea, and Vanflyta succeeded in entering the global market.