Rigel Pharmaceuticals & Forma Therapeutics Announce Licensing Agreement for Novel Mutant IDH1 Inhibitor

Rigel Pharmaceuticals, Inc. and Forma Therapeutics, Inc. recently announced they have entered into an exclusive, worldwide license agreement to develop, manufacture, and commercialize olutasidenib, an oral, small molecule inhibitor of mIDH1 being investigated for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML) and other malignancies.

In a Phase 2 registrational study of olutasidenib in patients with mIDH1 R/R AML, olutasidenib demonstrated a robust composite complete remission rate and duration of response and was well-tolerated. The US FDA has accepted Forma’s New Drug Application (NDA) for olutasidenib. The Prescription Drug User Fee Act (PDUFA) target action date is February 15, 2023.

“Olutasidenib is a potential market-leading treatment that we believe, based on the registrational Phase 2 data, can improve outcomes in patients with mIDH1+ relapsed or refractory acute myeloid leukemia, and is a strategic fit for our business,” said Raul Rodriguez, Rigel’s president and CEO. “This transaction expands our hematology-oncology portfolio and enables us to leverage our strong commercial capabilities to provide a potential new therapy for these patients who remain underserved despite currently available therapies.”

“The compelling efficacy and safety data generated to date highlight the potential for olutasidenib to transform the treatment of mIDH1+ R/R AML. The development and approval of olutasidenib, pending a favorable FDA decision, would represent an important milestone for Forma that highlights our R&D capabilities,” said Frank Lee, Forma’s president and CEO. “Given Rigel’s focus on hematologic diseases and cancers and the strength of their commercial infrastructure, we believe they are well-positioned to execute on our shared objective of delivering olutasidenib to patients in need.”

The registrational cohort of the open-label Phase 2 study evaluated olutasidenib as monotherapy in 153 mIDH1+ R/R AML patients. The primary efficacy-evaluable population of the cohort was comprised of 123 R/R AML patients, who received olutasidenib 150 mg twice daily at least six months prior to the interim analysis cutoff date of June 18, 2020 and had a centrally confirmed IDH1 mutation. The primary endpoint was a composite of a complete remission (CR) plus a complete remission with partial hematological recovery (CRh), 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 ANC >500/microliter).

Results from the interim analysis of the trial demonstrated a 33% CR+CRh in mIDH1+ R/R AML patients. Among those with CR+CRh, the estimated 18-month survival was 87% and the median duration of CR+CRh was not yet reached, with a more conservative sensitivity analysis indicating a median duration of 13.8 months. Importantly, these data provide compelling evidence of clinical efficacy with a durable response and a favorable tolerability profile, both of which we believe differentiates olutasidenib from other currently available treatment options for mIDH1+ R/R AML patients.

Olutasidenib was well-tolerated, with adverse events (AEs) being consistent with the late stage of disease and the heavily pre-treated population. A safety analysis for all 153 patients enrolled in the registrational Phase 2 study found the most common grade 3/4 (≥ 10%) treatment-emergent adverse events (TEAEs) were febrile neutropenia (20%), anemia (19%), thrombocytopenia (16%), and neutropenia (13%).

Updated data from the registrational study will be presented at an upcoming medical congress.

“The data from the Phase 2 registrational trial of olutasidenib demonstrated encouraging results, particularly on durability and survival, with median duration of response that appears to be longer than currently available treatment options and an 18-month survival rate among those with CR+CRh of 87%,” said Jorge E. Cortes, MD, Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator. “Given the trial’s compelling efficacy data in duration of response, the favorable tolerability profile, and the still limited treatment options of patients with mIDH1+ R/R AML, olutasidenib has the potential to be an important new treatment option for patients.”

Under the terms of the agreement, Forma will receive an upfront payment of $2 million, and is eligible to receive an additional $17.5 million upon the achievement of certain near-term regulatory, approval, and first commercial sale milestones.  In addition, Forma is eligible to receive a total of up to an additional $215.5 million in connection with the achievement of certain development and commercial milestones. Forma is also eligible to receive tiered royalties in the low-teens to mid-thirties. Moving forward, Rigel will be responsible for the potential launch and commercialization of olutasidenib in the US, and intends to work with potential partners to further develop and commercialize olutasidenib outside the US.

Olutasidenib is an oral, small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 9% of patients with AML. AML is a rapidly progressing cancer of the bone marrow and blood.  AML occurs primarily in adults and accounts for about 1% of all adult cancers. The American Cancer Society estimates that about 20,940 new cases, most in adults, arose in 2021 in the US alone. 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.

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. Rigel’s pioneering research focuses on signaling pathways that are critical to disease mechanisms. The company’s first FDA-approved product is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only oral spleen tyrosine kinase (SYK) inhibitor for the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. The product is also commercially available in Europe (TAVLESSE), the United Kingdom (TAVLESSE) and Canada (TAVALISSE) for the treatment of chronic immune thrombocytopenia in adult patients.

Fostamatinib is currently being studied in a Phase 3 clinical trial (NCT03764618) for the treatment of warm autoimmune hemolytic anemia (wAIHA); a Phase 3 clinical trial (NCT04629703) for the treatment of hospitalized high-risk patients with COVID-19⁵ and an NIH/NHLBI-sponsored Phase 3 clinical trial (ACTIV-4 Host Tissue Trial, NCT04924660) for the treatment of COVID-19 in hospitalized patients.

Rigel’s other clinical programs include its interleukin receptor-associated kinase (IRAK) inhibitor program, and a receptor-interacting serine/threonine-protein kinase (RIPK) inhibitor program in clinical development with partner Eli Lilly and Company. In addition, Rigel has product candidates in development with partners BerGenBio ASA and Daiichi Sankyo. For more information, visit www.rigel.com.