AACR 2019 – Xospata meets the conditions of its US approval

Survival data confirm the value of Astellas’s FLT3-targeting approach in acute myelogenous leukaemia.


Astellas’s FLT3 inhibitor Xospata looks even better than it did when it secured accelerated US approval last November, data revealed at an AACR plenary session today suggest. The results come from final analysis of the Admiral trial on the basis of which the drug got the US green light for relapsed/refractory AML patients carrying the FLT3 mutation.

Importantly, this is the first time survival data have been reported. Xospata (gliteritinib) has been shown to extend median overall survival by 3.7 months – no mean feat in a disease as intractable as AML – representing a 36% reduction in risk of death, with a high level of statistical significance.

At an AACR press conference today Dr Alexander Perl, from the University of Pennsylvania, called the study practice-changing, and said it established Xospata as a standard of care in this patient population.

He also reported improved remission rates. Xospata was approved on the basis of interim data that showed a rate of complete response with full or partial recovery of blood counts of 21%; at final readout this amounted to 34%.

This improvement was partly down to more patients in the active cohort’s final analysis (247) than at interim (138), but it was clearly also due to some initially non-responding subjects going into remission later. The Xospata result by the strict definition of CR also rose, from 12% at interim to 21% in the AACR presentation.

Final data from the Admiral trial (NCT02421939)
  Xospata (n=247) Chemo control (n=124)
Median overall survival 9.3mth 5.6mth
Hazard ratio 0.64
p value 0.0007
CR/CRh* rate 34.0% 15.3%
p value 0.0106
Source: AACR; *complete remission with full or partial haematological recovery.

AML remains a very tough haematological cancer to treat, but progress has been made in recent years thanks to identification of genetic markers that drive the disease.

Thus Jazz’s Vyxeos is approved in therapy-related AML or AML with myelodysplasia-related changes, while Pfizer’s Mylotarg has a label specifically in CD33-positive disease.

The FLT3 gene is expressed in normal bone marrow cells, but its mutation is thought to drive some 30% of AMLs, making it the most commonly mutated gene in AML. Xospata has shown activity against two specific mutations: FLT3 internal tandem duplication and tyrosine kinase domain mutation.

There are other FLT3-specific approaches, too, including Novartis’s Rydapt, which is approved in FLT3 mutants even though its mechanism is now thought to be broader. Daiichi Sankyo’s FLT3 inhibitor quizartinib is awaiting approval, while Allogene is developing ALLO-819, an allogeneic anti-FLT3 CAR-T therapy.

EvaluatePharma sellside consensus sees Xospata sales hitting $538m in 2024. No fewer than four other phase III studies are ongoing, including in post-transplant maintenance and in first-line chemotherapy-ineligible subjects, so Astellas is serious about reaching these numbers.

This is an updated version of an earlier story.

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