Full Press Release Details
FDA GRANTS APPROVAL OF IDHIFA , THE FIRST ORAL
TARGETED THERAPY FOR ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA AND AN IDH2 MUTATION
IDHIFA is the first and
only oral, targeted inhibitor of IDH21
FDA approval of IDHIFA was based on
results from the phase I/II AG-221 AML-001 study including safety, rate and duration of complete response (CR) or CR with partial hematologic recovery (CRh) and rate of conversion to transfusion independence1
Relapsed and refractory AML is a debilitating disease with a significant unmet
Summit, NJ, and Cambridge, Mass., August 1, 2017 Celgene Corporation
(NASDAQ:CELG) and Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) today announced that IDHIFA (enasidenib) was granted approval from the U.S. Food and Drug Administration (FDA) for the treatment of
adult patients with relapsed or refractory AML (R/R AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA approved test.1 IDHIFA, an oral targeted inhibitor of the IDH2
enzyme, is the first and only FDA-approved therapy for patients with R/R AML and an IDH2 mutation, which represents between 8 and 19 percent of AML patients.3
The FDA approval of IDHIFA provides the first-ever treatment option for patients living with relapsed or refractory AML and an IDH2 mutation. We
appreciate the FDA s efforts to expedite the availability of IDHIFA for patients with this devastating disease weeks ahead of the PDUFA date, said Mark Alles, Chief Executive Officer of Celgene. This milestone further illustrates
the value of Celgene s unique distributed research model. Our partnership with Agios is an exceptional example of how Celgene and its collaborators can positively impact the lives of patients with high unmet needs.
AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with more than 21,000
new cases estimated in the U.S. each year.4,5,6 The majority of patients with AML eventually experience relapse. Relapsed or refractory AML has a poor prognosis.6 For 8 to 19 percent of AML patients, the mutated IDH2 enzyme blocks normal blood cell development and results in an overabundance of immature blood
The FDA approval of IDHIFA just four years after entering the clinic is the first of
what we expect to be multiple first-in-class precision medicines for patients with cancer and rare genetic diseases from our productive discovery engine, said David Schenkein, M.D., Chief Executive Officer of Agios. We look forward to
working closely with Celgene to co-commercialize IDHIFA and provide access for patients in the U.S. with this devastating disease.
complex, heterogeneous disease, which is particularly difficult to treat in the relapsed or refractory setting, said Martin Tallman, M.D., Hematologic Oncologist and Chief, Leukemia Service at Memorial Sloan Kettering Cancer Center. IDH2
mutations inhibit the normal maturation of myeloid cells, so having a treatment that targets this mechanism is promising for patients and encouraging to us as physicians who have it as our goal to provide options for every patient.
Demonstrating Clinical Benefit & Safety with
The FDA approval was based on the clinical data from an open-label, single-arm,
multicenter, two-cohort clinical trial of adult patients with R/R AML and an IDH2 mutation (Study AG221-C-001, NCT01915498). IDHIFA was approved concurrently with the Abbott RealTime IDH2 companion diagnostic test, which is FDA-approved
as an aid in identifying AML patients for treatment with IDHIFA.
The efficacy of IDHIFA was evaluated in 199 adult patients with R/R AML and an IDH2
mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime IDH2 test. IDHIFA was given orally at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to
manage side effects. Patients had a median age of 68 years (range of 19 to 100) and received a median of two prior anticancer regimens (ranging from one to six). More than half (52%) were refractory to previous therapy.
In this trial, IDHIFA demonstrated a combined complete response or complete response with partial hematologic improvement (CR/CRh) rate of 23% (n=46) (95% CI:
18%, 30%). Median duration of CR/CRh was 8.2 months (95% CI: range 4.3, 19.4). For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5 months) and the median time to best response of CR/CRh was
3.7 months (range, 0.6 to 11.2 months). Of patients achieving a CR/CRh, 85% (39 of 46 patients) did so within six months of initiating IDHIFA.
Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and
platelet transfusions during any 56-day post-baseline period. Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
The safety of IDHIFA was evaluated in 214 patients with R/R AML and an IDH2 mutation. The median duration of exposure to IDHIFA was 4.3 months (range 0.3 to
23.6). The 30-day and 60-day mortality rates observed with IDHIFA were 4.2% (9/214) and 11.7% (25/214), respectively.
In the clinical trial, 14% of
patients treated with IDHIFA experienced differentiation syndrome, which can be fatal if not treated. IDHIFA can cause fetal harm if administered to pregnant women. The most common adverse reactions
( 20%) of any grade were nausea, vomiting, diarrhea, elevated bilirubin and decreased appetite. Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions ( 2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
IDHIFA (enasidenib) is indicated for the
treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.
Important Safety Information
WARNINGS AND PRECAUTIONS
Differentiation Syndrome:
See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5
months after IDHIFA initiation. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may
recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until
signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.
Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise
females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while
receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.
Many drugs are excreted in
human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.
Please see full Prescribing Information, including Boxed WARNING
About Acute Myeloid Leukemia (AML)
AML, a cancer of blood
and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly
increases with age, and according to SEER, the median age of onset is 68.4 Some patients do not respond to chemotherapy and progress to relapsed/refractory AML.6 The five-year relative survival rate for AML is approximately 26.9% based on data from SEER 18 between 2007-2013.4 Overall survival for patients
who become relapsed or refractory to initial therapy is estimated at less than six months.2,6 IDH2 mutations are present in about 8 to 19 percent of AML cases.3
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery,
development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more
information, please visit www.celgene.com. Follow Celgene on social media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
About Celgene Patient Support
At Celgene, we promise that patients have the opportunity to take advantage of significant advances in medicine that may help them live longer, better and
healthier lives. Accordingly, we work to help ensure access to the clinical benefits of our innovative therapies. For patients receiving Celgene therapies, irrespective of their insurance situation, Celgene Patient Support offers access information and support, which includes helping patients understand their insurance coverage and providing information about potential financial assistance options. Visit
www.celgenepatientsupport.com for additional information.
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic diseases through scientific leadership in the
field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has multiple first-in-class investigational medicines in clinical and/or preclinical development. All Agios programs focus on
genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company s website at www.agios.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be
identified by the words expects, anticipates, believes, intends, estimates, plans, will, outlook and similar expressions. Forward-looking statements are
based on management s current plans, estimates, assumptions and projections, and speak only as of the date they are made. Neither Celgene nor Agios undertake any obligation to update any forward-looking statement in light of new information or
future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond each company s control. Actual results or outcomes may
differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in the Annual Report on Form 10-K and other reports of each company filed with the
Securities and Exchange Commission.
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Kendra Adams, 617-844-6407
Senior Director, Investor &
Senior Manager, Investor & Public Relations
Holly Manning, 617-844-6630
Associate Director, Corporate