8-K: Syndax Pharmaceuticals' Revuforj Receives FDA Approval for KMT2A-Translocated Leukemia

The FDA has approved Syndax Pharmaceuticals' Revuforj as the first and only menin inhibitor for treating relapsed or refractory acute leukemia with a KMT2A translocation in adult and pediatric patients.

Summary

• The U.S. Food and Drug Administration (FDA) has approved Revuforj (revumenib) for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation.
• This approval makes Revuforj the first and only menin inhibitor available for this specific type of leukemia.
• The approval is based on data from the AUGMENT-101 clinical trial, which showed a 21% complete remission rate plus complete remission with partial hematological recovery (CR+CRh) in 104 patients.
• The median duration of CR+CRh was 6.4 months, and the median time to CR or CRh was 1.9 months.
• The drug will be available in 110 and 160 mg tablets in November 2024, with 25 mg tablets expected in late first quarter or early second quarter of 2025.
• An oral solution will be available through an expanded access program for patients under 40 kg before the 25mg tablets are available.
• Syndax has established SyndAccess, a program to provide support and financial assistance to patients.

Sentiment

Score: 9

Explanation: The document is highly positive due to the FDA approval of a novel drug with promising clinical trial results, addressing a significant unmet medical need. The company is well-prepared for launch and has a patient support program. However, there are some risks associated with the drug, such as differentiation syndrome and QTc prolongation, which are well-disclosed.

Positives

• Revuforj represents a major breakthrough as the first menin inhibitor for this specific type of leukemia.
• The clinical trial data showed a significant improvement in remission rates compared to historical outcomes.
• The drug has received Breakthrough Therapy and Fast Track designations, as well as Priority Review from the FDA.
• Syndax has a patient support program, SyndAccess, to help with access and financial assistance.
• The drug is expected to be available relatively quickly after approval.

Negatives

• Revuforj can cause differentiation syndrome, which can be fatal.
• QTc interval prolongation is another potential adverse reaction.
• There are several common adverse reactions, including hemorrhage, nausea, and increased phosphate levels.
• Fatal adverse reactions occurred in 3% of patients in the clinical trial.
• Serious adverse reactions were reported in 73% of patients.

Risks

• Differentiation syndrome is a serious risk, requiring immediate corticosteroid therapy and monitoring.
• QTc interval prolongation requires careful monitoring and potential dose adjustments.
• The drug has several potential drug interactions that need to be managed.
• There is a risk of embryo-fetal toxicity, requiring contraception during treatment.
• The drug may impair fertility.

Future Outlook

Syndax plans to make Revuforj commercially available this month and is committed to advancing its development across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML. They are also conducting multiple trials of revumenib in combination with standard-of-care agents.

Management Comments

• Michael A. Metzger, Chief Executive Officer of Syndax, stated that the approval of Revuforj is a remarkable achievement and reflects the dedication of everyone involved.
• He also mentioned that Syndax is well-prepared to launch Revuforj this month and is committed to rapidly advancing its development.
• Ghayas C. Issa, M.D., Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center, noted that the approval is a major breakthrough and represents a substantial improvement over previously available therapies.

Industry Context

This approval is significant as it introduces the first menin inhibitor for a specific type of acute leukemia, addressing a critical unmet need in a patient population with a poor prognosis. This could set a new standard of care for KMT2A-translocated leukemia and potentially impact the treatment landscape for other related leukemias.

Comparison to Industry Standards

• Historically, patients with relapsed or refractory KMT2A-translocated acute leukemia have had very poor outcomes, with a median overall survival of less than one year after frontline therapies and only 5% achieving complete remission with third-line treatment or beyond.
• The 21% complete remission rate plus complete remission with partial hematological recovery (CR+CRh) achieved with Revuforj in the AUGMENT-101 trial represents a significant improvement over these historical benchmarks.
• While specific comparisons to other menin inhibitors are not possible as this is the first approved drug in this class, the results are being compared to standard of care treatments for this type of leukemia.
• The median duration of CR+CRh of 6.4 months is also a notable improvement compared to the very short survival times seen with previous treatments.

Stakeholder Impact

• Shareholders will likely react positively to the FDA approval and commercial launch of Revuforj.
• Patients with relapsed or refractory KMT2A-translocated acute leukemia will have a new treatment option with improved outcomes.
• Clinicians will have a new tool to treat this aggressive form of leukemia.
• Employees of Syndax will be involved in the commercialization and further development of Revuforj.

Next Steps

• Syndax will launch Revuforj commercially in the United States.
• The company will continue to advance the development of Revuforj across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML.
• Syndax will continue to conduct clinical trials of revumenib in combination with standard-of-care agents.
• The company will make 110 and 160 mg tablets available in November 2024.
• The company will make 25 mg tablets available in late first quarter or early second quarter of 2025.
• An oral solution will be available through an expanded access program for patients under 40 kg before the 25mg tablets are available.

Key Dates

Keywords

Revuforj, revumenib, menin inhibitor, KMT2A translocation, acute leukemia, FDA approval, hematopoietic stem cell transplantation, AUGMENT-101, relapsed, refractory, Syndax Pharmaceuticals, differentiation syndrome, QTc prolongation