A new therapy for certain adults with relapsed or refractory acute myeloid leukemia (AML), developed by Celgene Corp. and Agios Pharmaceuticals Inc., has won earlier-than-expected FDA approval following a priority review.

The oral therapy, Idhifa (enasidenib), is the first and only one the agency has approved to address AML patients with an isocitrate dehydrogenase-2 (IDH2) mutation, a group accounting for between 8 and 19 percent of AML patients, or about 1,200 to 1,500 individuals in the U.S. Alongside it, the FDA green-lighted an Abbott-developed companion diagnostic that can detect IDH2 gene mutations, which runs on Abbott's m2000rt Realtime System, a PCR testing automation system.

Agios had previously worked with Foundation Medicine Inc. to find patients most likely to respond to its IDH1 and IDH2-targeting candidates and "to develop and potentially commercialize diagnostic products" for those programs, but picked Abbott as its commercial partner in October 2016. Agios spokeswoman Holly Manning said the Foundation collaboration was "more focused on using their platform in our clinical trials."

Though a relatively small market for Celgene, analyst forecasts compiled by Cortellis project the therapy could generate $100 million in 2018 sales, peaking in 2021 with $456 million in annual revenue, a ramp-up likely tied to expectations that the partners could expand into first-line treatment of AML.

Mutations in IDH2, a critical metabolic enzyme, result in elevated levels of the oncometabolite 2-hydroxyglutarate (2HG), which prevents differentiation of myeloblasts, leading to tumor formation and progression. By inhibiting IDH2, Idhifa (formerly AG-221) aims to reduce 2HG levels and restore myeloblast differentiation. (See BioWorld Today, April 8, 2014.)

Patients in the pivotal study were treated with Idhifa for a median of 4.3 months. At a monthly wholesale acquisition cost of $24,872, that would equate to a cost of about $107,000 per patient.

Celgene spokesman Greg Geissman said the company is proactively working with U.S. payers on patient-centric agreements designed to provide immediate access to the medicine with no out-of-pocket costs for eligible patients, other than those covered by federal health care programs.

Summit, N.J.-based Celgene, which completed its new drug application in late December 2016, licensed Idhifa from Cambridge, Mass.-based Agios as part of a 2010 collaboration agreement. The oral medicine, the first to emerge from the partnership, works by blocking several enzymes that promote cell growth.

Celgene has worldwide development and commercialization rights for Idhifa. Agios is eligible to receive up to $120 million in payments assuming achievement of certain milestones and royalties on net sales. Both companies will work to market the drug in the U.S., though Celgene will reimburse Agios for costs incurred for its part of those efforts.

The approval was based on the results of a single-arm trial of 199 patients with relapsed or refractory AML who had IDH2 mutations as detected by the Realtime IDH2 Assay. The study measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment, or complete remission (CR), as well as patients with no evidence of disease and partial recovery of blood counts after treatment, called CR with partial hematologic recovery, or CRh, the FDA said.

With a minimum of six months of treatment, 19 percent of patients experienced CR for a median 8.2 months, and 4 percent of patients experienced CRh for a median 9.6 months. Of the 157 patients who required transfusions of blood or platelets due to AML at the start of the study, 34 percent no longer required transfusions after treatment with Idhifa, according to the agency.

Common side effects of Idhifa include nausea, vomiting, diarrhea, increased levels of bilirubin and decreased appetite.

The approved label includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can be fatal if not treated. The agency also advised pregnant or breastfeeding women against taking the therapy due to risks of harming a developing fetus or newborn baby.

Idhifa received both FDA fast track and orphan status for AML. It also has EMA orphan status.

About 21,380 people are expected to be diagnosed with the fast-progressing bone marrow cancer this year. Despite treatment, the majority of them will eventually experience relapse. Both induction and consolidation therapies typically include chemo, though at differing doses. Allogeneic or autologous stem cell transplants are also used during consolidation therapy for younger patients. About 10,590 people with the condition are expected to die of the disease in 2017.

Even after Tuesday's approval, Celgene and Agios still have a significant slate of partnered assets in development. First, they're working to expand the number of patients – and, of course, the market – addressable by enasidenib, testing it in combination with Vidaza (azacitidine) and, separately, with a standard chemotherapy regimen of cytarabine and daunorubicin, in newly diagnosed AML patients. They're also studying the orally available IDH1 inhibitor ivosidenib (AG-120) in a variety of cancers that harbor an IDH1 mutation, including front-line and relapsed/refractory AML. Another candidate, the pan-IDHm inhibitor AG-881, is under investigation for the treatment of glioma with IDH mutations.

Other companies are also working on precision treatments for AML. Astellas Pharma Inc., of Tokyo, is investigating gilteritinib in various patient populations through several planned and already started phase III trials, including the registrational Admiral experiment in relapsed/refractory FLT3-positive AML. Glycomimetics Inc., of Rockville, Md., is advancing GMI-1271, an E-selectin antagonist for relapsed/refractory AML. And, in May, Novartis AG, of Basel, Switzerland, gained FDA approval for Rydapt (midostaurin), a therapy for people with newly diagnosed AML positive for FLT3 mutation. A positive opinion recommending approval of the medicine in Europe arrived in July. (See BioWorld Today, May 1, 2017.)

Shares of Agios (NASDAQ:AGIO) closed Tuesday at $58.65, up $2.71, while shares of Celgene (NASDAQ:CELG) closed at $135.18, down 23 cents.

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