Rigel Pharmaceuticals’ isocitrate dehydrogenase-1 mutant (mIDH1) targeting small molecule inhibitor Rezlidhia (olutasidenib) has won US Food and Drug Administration (FDA) approval for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML).
The oral small molecule inhibitor is indicated for patients with an IDH1 mutation as detected by the Abbott RealTime IDH1 Assay, which received FDA approval alongside Rezlidhia.
Rezlidhia is designed to inhibit mIDH1 to reduce levels of 2-hydroxyglutarate, a metabolite that is overproduced due to mutations in IDH1 resulting in its accumulation, to restore normal differentiation of myeloid cells. Approximately eight percent of AMLs harbor an IDH1 mutation, and 12 percent have mutations in IDH2.
AML is an aggressive cancer of the blood and bone marrow involving the rapid proliferation of aberrant, undifferentiated myeloid cells. The cancer progresses rapidly and has had limited treatment options in the past, primarily consisting of intensive induction chemotherapy with cytarabine (ara-C) and an anthracycline such as daunorubicin (daunomycin) or idarubicin.
As such, the prognosis of AML is relatively poor with a five-year survival rate of just over 20 percent (although the statistics are improving with new treatments and better supportive care). Allogeneic stem cell transplantation can be an option for patients who achieve complete remission and are at high risk of relapse. While it can be curative, allogeneic stem cell transplantation is associated with a risk of graft-versus-host disease (GVHD) and is generally better suited for patients who are not very weak or fragile.
Approximately 50 percent of AML patients will relapse within approximately two years, on average, and treating relapsed or refractory AML has been a major challenge.
Targeted therapies like Novartis’ Rydapt (midostaurin), which targets mutations in the FMS-like tyrosine kinase 3 receptor (FLT3) — are now approved to be given with chemo and could help improve outcomes.
Rezlidhia’s approval came a couple of months ahead of its FDA target date of February 15, 2023.
“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 in a press release from the company.
“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 hematology-oncology portfolio.”
The FDA approval of Rezlidhia was based on data from a Phase II study evaluating Rezlidhia as a monotherapy in 147 adult AML patients with mIDH1. Results from the trial revealed a 35 percent complete remission rate with a median duration of response of about 26 months. The median time to complete remission was 1.9 months.
Rezlidhia will be going up against Servier’s Tibsovo (ivosidenib), which the FDA approved as a monotherapy in 2018. At the time, Agios owned the drug and last year, Servier bought out the company in a $1.8 billion deal. This year, the FDA approved Tibsovo in combination with azacytidine chemotherapy for newly diagnosed AML with IDH1 mutation in adults 75 years of age or older, or who have comorbidities that prevent them from receiving intensive chemotherapy.
In August, Rigel and Forma Therapeutics, Inc. inked an exclusive, worldwide license agreement to develop, manufacture and commercialize Rezlidhia. Under the terms of the deal, Rigel said it will be responsible for launching and commercializing the drug in the US, and also hopes to work with potential partners to further develop and commercialize it outside the country.