AML cells
The US Food and Drug Administration (FDA) has granted fast track designation to CX-01 as a treatment for patients older than 60 receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin that is thought to enhance chemotherapy by disrupting the adhesion of leukemia cells in the bone marrow.
CX-01 inhibits the activity of HMGB1, disrupts the CXCL12/CXCR4 axis, and neutralizes the activity of platelet factor 4. HMGB1 has been implicated in autophagy, a mechanism by which cells withstand the effects of chemotherapy.
The CXCL12/CXCR4 axis is thought to be involved in protecting leukemia cells from chemotherapy. And platelet factor 4 inhibits bone marrow recovery after chemotherapy.
CX-01 research
Cantex Pharmaceuticals, Inc., is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances in February.
The study enrolled 12 adults with newly diagnosed AML. Patients had good-risk (n=3), intermediate-risk (n=5), and poor-risk (n=4) disease.
They received CX-01 as a 7-day continuous infusion, along with standard induction chemotherapy (cytarabine and idarubicin).
Eleven patients (92%) achieved morphologic complete remission after one cycle of induction. This includes two patients who did not complete induction. All patients received subsequent therapy—consolidation, salvage, or transplant—on- or off-study.
At a median follow-up of 24 months, 8 patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage.
The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events (AEs) in five patients. Most of these AEs were considered unrelated to CX-01, but a case of grade 4 sepsis was considered possibly related to CX-01.
Transient, asymptomatic, low-grade elevations of liver transaminases observed during induction were considered possibly related to CX-01. There were also transient, asymptomatic, grade 3-4 liver transaminase elevations observed during consolidation that were considered possibly related to CX-01.
The researchers said the most frequent nonserious AEs were hematologic toxicities, infectious complications, and organ toxicity complications resulting from treatment and/or the underlying leukemia.
About fast track, orphan designations
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.