Rigel Pharmaceuticals, Inc. announced that the US Food and Drug Administration (FDA) has approved Rezlidhia (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Rezlidhia is an oral, small molecule, inhibitor of mutated IDH1 designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells.

"Rezlidhia is a novel, non-intensive monotherapy treatment in the relapsed/refractory AML setting demonstrating a CR+CRh rate of 35% in patients with over 90% of those responders in complete remission. The 25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options," said Jorge E. Cortes, M.D., director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and phase 2 trial investigator. "Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, Rezlidhia may provide an effective, new treatment option with a well characterized safety profile."

The FDA approval was supported by data from the open-label phase 2 registrational study evaluating Rezlidhia monotherapy at a dose of 150 mg twice daily in 153 mIDH1 R/R AML patients. The efficacy-evaluable population was 147 patients who initiated Rezlidhia at least six months prior to the interim analysis cutoff date of June 18, 2021, and who had a centrally confirmed IDH1 mutation. The primary endpoint was a composite of a complete remission (CR) plus a complete remission with partial haematological recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).

Results from the trial demonstrated a 35% (51/147) CR+CRh rate in mIDH1 R/R AML patients, with a median duration of response of 25.9 months. The median time to CR or CRh was 1.9 months. Of the patients who achieved the primary endpoint of CR+CRh, 92% (47/51) were CR with a median duration of response of 28.1 months. Rezlidhia was well tolerated in the study with an adverse event profile largely characteristic of symptoms or conditions experienced by patients with AML undergoing treatment. Differentiation syndrome was observed in 16% of patients and was manageable in most cases with dose interruption and corticosteroids. Hepatotoxicity, presenting as increases in liver function parameters, occurred in 23% of patients and most cases were manageable with dose modifications.

"We are delighted by the approval of Rezlidhia based on the strength of data supporting the efficacy and safety of the product," said Raul Rodriguez, Rigel's president and CEO. "Rezlidhia provides a new and important, oral therapy option for patients who typically have a poor clinical outcome. Additionally, this approval greatly strengthens and expands Rigel's commercial haematology-oncology portfolio. I would like to extend our sincerest thanks to all the patients, their families and caregivers, the doctors, the FDA, and our team members who have all contributed to the approval of Rezlidhia."

In August 2022, Rigel and Forma Therapeutics, Inc. announced they entered an exclusive, worldwide license agreement to develop, manufacture and commercialize Rezlidhia. Under the terms of the agreement, Rigel will be responsible for the launch and commercialization of Rezlidhia in the US, and intends to work with potential partners to further develop and commercialize the product outside the US.

Acute myeloid leukaemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 per cent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,050 new cases, most in adults, in 2022.

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukaemia cells in the bone marrow. Refractory AML, which affects between 10 and 40 per cent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment. Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

Rezlidhia is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukaemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Rigel Pharmaceuticals, Inc. is a biotechnology company dedicated to discovering, developing and providing novel small molecule drugs that significantly improve the lives of patients with hematologic disorders, cancer, and rare immune diseases