Introduction to Enasidenib Mesylate
Enasidenib mesylate, marketed as IDHIFA, is an anti-cancer agent specifically designed to target the isocitrate dehydrogenase-2 (IDH2) mutation. It is approved for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who have this mutation[1][3][4].
Clinical Trials and Approval
FDA Approval
Enasidenib mesylate received regular approval from the U.S. Food and Drug Administration (FDA) on August 1, 2017, for the treatment of adult patients with relapsed or refractory AML with an IDH2 mutation. This approval was based on the results of Study AG221-C-001, an open-label, single-arm, multicenter clinical trial involving 199 adults. The study demonstrated significant complete response (CR) and complete response with partial hematologic recovery (CRh) rates, with a median duration of response of 8.2 months[1].
Ongoing and Future Clinical Trials
In addition to its approved use in AML, enasidenib mesylate is being studied for various other indications, including:
- Clonal cytopenia of undetermined significance (CCUS)
- Hematologic malignancies such as untreated AML and myelodysplastic syndrome (MDS)
- Chronic myelomonocytic leukemia (CMML)
- Myeloproliferative neoplasm
- Solid tumors
- Malignant sinonasal and skull base tumors
- Chondrosarcoma, currently in Phase II clinical trials[2][3].
Market Analysis
Current Market Status
Enasidenib mesylate was authorized under a Notice of Compliance with conditions (NOC/c) in Canada in 2019 but is set to be withdrawn from the Canadian market as of June 30, 2023, due to its failure to demonstrate improved overall survival (OS) compared to conventional care regimens in a Phase 3 confirmatory study. However, it remains available through Health Canada’s Special Access Program (SAP) for patients who require continued treatment[4].
Budget Impact Analysis
A budget impact analysis conducted in the U.S. estimated the financial implications of adding enasidenib to a health plan formulary. The study suggested that while the introduction of enasidenib would increase drug acquisition and diagnostic testing costs, it would slightly decrease costs associated with administration, transfusions, and adverse events. The additional per member per month (PMPM) costs were estimated to be minimal, plateauing at USD 0.011 in the third year post-introduction[5].
Market Projections
Given the specific target population of patients with IDH2 mutations, the market for enasidenib mesylate is niche but significant. Here are some key projections:
- Patient Eligibility: Approximately 15 patients per year in a health plan with 5 million covered lives are estimated to be eligible for treatment with enasidenib for relapsed or refractory AML with an IDH2 mutation[5].
- Market Share: The drug's market share is expected to grow as more patients are diagnosed with IDH2 mutations and as the drug is explored for additional indications.
- Cost Implications: While the drug acquisition costs are high, the overall budget impact is expected to be manageable due to the reduction in other medical costs such as transfusions and adverse event management[5].
Safety and Efficacy
Safety Profile
Enasidenib mesylate has a notable safety profile, with common adverse reactions including nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite. Differentiation syndrome, a potentially fatal condition, occurred in 14% of patients and is highlighted with a boxed warning in the prescribing information[1].
Efficacy
The efficacy of enasidenib mesylate in treating relapsed or refractory AML with an IDH2 mutation has been demonstrated through clinical trials. The drug achieved a complete response (CR) or complete response with partial hematologic recovery (CRh) in 23% of patients, with a median duration of response of 8.2 months[1].
Future Directions
Expanding Indications
Enasidenib mesylate is under investigation for several other hematologic and solid tumor malignancies. The Phase II trial for chondrosarcoma is a significant example of its potential expansion into new therapeutic areas[2].
Regulatory Considerations
The withdrawal from the Canadian market highlights the importance of ongoing clinical trials and the need for drugs to demonstrate sustained clinical benefit. Healthcare professionals are advised not to initiate enasidenib in new patients but to consider continued treatment through special access programs for patients already benefiting from the drug[4].
Key Takeaways
- Approved Use: Enasidenib mesylate is approved for treating adult patients with relapsed or refractory AML with an IDH2 mutation.
- Clinical Trials: Ongoing trials explore its use in various other malignancies, including chondrosarcoma.
- Market Analysis: The drug has a manageable budget impact despite high acquisition costs, mainly due to reduced other medical expenses.
- Safety and Efficacy: It has a notable safety profile and demonstrated efficacy in clinical trials.
- Future Directions: Expanding indications and regulatory considerations are crucial for its continued use and market presence.
FAQs
What is enasidenib mesylate used for?
Enasidenib mesylate is used to treat adult patients with relapsed or refractory acute myeloid leukemia (AML) who have an isocitrate dehydrogenase-2 (IDH2) mutation.
What are the common side effects of enasidenib mesylate?
Common side effects include nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite. Differentiation syndrome is a serious potential side effect.
Why is enasidenib mesylate being withdrawn from the Canadian market?
Enasidenib mesylate failed to demonstrate improved overall survival compared to conventional care regimens in a Phase 3 confirmatory study.
What other conditions is enasidenib mesylate being studied for?
It is being studied for clonal cytopenia of undetermined significance (CCUS), untreated AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasm, solid tumors, and chondrosarcoma.
How does enasidenib mesylate impact healthcare costs?
The introduction of enasidenib mesylate slightly increases drug acquisition and diagnostic testing costs but reduces costs associated with administration, transfusions, and adverse events, resulting in a minimal overall budget impact.
Sources
- FDA: FDA granted regular approval to enasidenib for the treatment of relapsed or refractory AML.
- Pharmaceutical Technology: Enasidenib mesylate by Bristol-Myers Squibb for Chondrosarcoma.
- National Cancer Institute: Enasidenib Mesylate.
- Bristol-Myers Squibb: Important Safety and Efficacy Information on IDHIFA® (Enasidenib Mesylate).
- RTI International: Budget impact analysis of enasidenib treatment in patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation.
