Syndax Pharmaceuticals’ Revuforj (revumenib) has won US Food and Drug Administration (FDA) approval for the treatment of relapsed or refractory (R/R) acute leukemia in patients aged one year and older who have a lysine methyltransferase 2A (KMT2A, formerly MLL) gene translocation.
The approval marks the first menin inhibitor to receive FDA clearance, offering a novel therapeutic option for this challenging leukemia subtype.
Menin is a protein involved in gene regulation and cellular growth, playing a critical role in the interaction between the KMT2A gene and its fusion partners, which drive the development of certain aggressive cancers, particularly leukemias.
Revuforj’s approval was granted six weeks ahead of schedule, making it Syndax’s second FDA new drug approval in just three months.
In August, Syndax, in collaboration with commercial partner Incyte, received FDA approval for Niktimvo (axatilimab), a CSF-1R inhibitor designed to treat chronic graft-versus-host disease (cGVHD) in patients who have failed at least two prior lines of systemic therapy.
In a conference call last week, Michael Metzger, CEO of Syntax said, “The FDA approval of two first-in-class medicines in one year is an absolutely remarkable achievement for a biotech company of our size and reflects the skill and dedication of our entire organization and our network of collaborators.”
The Massachusetts-based company, which opened its doors 19 years ago, had 184 employees to start off the year, a significant increase from 107 at the start of 2023.
Related: Niktimvo (Axatilimab) Approved as First-in-Class Therapy for Chronic GVHD
As Syndax enters its commercial phase, it is rapidly expanding its workforce. To support these efforts, Syndax secured a deal with Royalty Pharma earlier this month, receiving $350 million upfront in exchange for 13.8 percent of US sales revenue from Niktimvo. The agreement will conclude once Royalty Pharma achieves 2.35 times its initial investment.
Revuforj’s approval follows a setback just last week for Syndax, where results from a Phase I/II trial of revumenib in patients with R/R mutant NPM1 acute myeloid leukemia (AML) showed that although the trial achieved its primary endpoint, with 12 out of 64 patients attaining complete remission, they fell short of investor expectations.
Since the announcement, Syndax’s stock price has dropped 26 percent, declining from $21.78 to $16.08, with the recent FDA approval offering only a modest recovery.
Syndax said revumenib was previously granted Orphan Drug designation for the treatment of AML, acute lymphoblastic leukemia (ALL) and acute leukemias of ambiguous lineage (ALAL) by the FDA and for the treatment of AML by the European Commission.
The agency also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement (KMT2Ar) or NPM1 mutation and Breakthrough Therapy designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.
According to Syndax, the US patient population for Revuforj’s approved indication is approximately 2,000. KMT2Ar leukemias are associated with a long-term survival rate of less than 60 percent across all age groups, progression-free survival (PFS) ranging from 30 percent to 40 percent and overall survival (OS) below 25 percent.
Rearrangements of the KMT2A gene drive a particularly aggressive form of acute leukemia, characterized by a poor prognosis and high relapse rates.
Over 95 percent of patients with KMT2Ar acute leukemia exhibit a KMT2A translocation. Despite receiving standard frontline therapies, more than half of these patients experience relapse, with a median OS of less than one year. For those undergoing third-line or later treatments, the outlook is even grimmer — only five percent achieve complete remission, and the median OS drops to less than three months.
The FDA’s decision was based on data from the Phase I/II AUGMENT-101 trial, which evaluated revumenib in 104 patients with R/R acute leukemia harboring a KMT2A translocation.
The study reported a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 21 percent, with a median duration of response of 6.4 months. The median time to CR or CRh was 1.9 months.
Out of the 104 patients, 24 became eligible for hematopoietic stem cell transplantation (HSCT).
“The approval of Revuforj is a remarkable achievement that reflects the dedication and tenacity of everyone involved, especially the patients and clinicians who participated in our trial and our talented Syndax team,” said Michael A. Metzger, CEO of Syndax. “We are well-prepared to launch Revuforj this month and we are committed to rapidly advancing the development of Revuforj across the treatment continuum for KMT2A-rearranged acute leukemias and mutant NPM1 AML.”
Revuforj is expected to be available in the US market later this month.
Syndax said it anticipates that the 110 mg and 160 mg tablets of Revuforj will be available for purchase in the US through a network of specialty distributors and pharmacies starting in November.
The 25 mg tablets, designed for patients weighing less than 40 kg, are expected to become commercially available by late Q1 or early Q2 of 2025, the company said. In the interim, an oral solution of revumenib will be accessible through an expanded access program to facilitate treatment for patients under 40 kg until the 25 mg tablets are launched.
Syndax is also pursuing additional approvals for revumenib in other leukemia subtypes and is hoping to expand the labels for both Revuforj and Niktimvo, hoping to hit blockbuster potential for them.
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