In 1995, the FDA approved Amgen ’s G-CSF (granulocyte colony-stimulating factor) as the first and only treatment for the rare blood disorder chronic neutropenia. Nearly three decades later, X4 Pharma aims to add a second therapy to the mix as it gears up for a registrational trial next year.

X4 Pharma plans to run a Phase III trial of mavorixafor in chronic neutropenia in H2 2023, CEO Paula Ragan tells Clinical Trials Arena. The international, placebo-controlled trial will likely enroll 80–100 patients across two arms over the course of an 8–12 month trial, she adds.

Chronic neutropenia is characterized by low levels of neutrophils, a type of white blood cell that helps the body fight off infections. Mavorixafor, an oral small molecule antagonist of chemokine receptor CXCR4, causes neutrophils to egress from bone marrow and enter the bloodstream. The goal, Ragan explains, is for oral mavorixafor to reduce or possibly replace use of injectable G-CSF as the standard of care.

As a primary endpoint, the planned Phase III trial will assess neutrophil count, which is a strong surrogate marker of chronic neutropenia, Ragan says. Secondary endpoints will measure the frequency and severity of infections, ensuring X4 Pharma builds a broad dataset to demonstrate how mavorixafor helps patients, she adds.

Ongoing trials of mavorixafor

As X4 Pharma prepares for the registrational trial, the biotech is also expanding an ongoing Phase Ib trial in chronic neutropenia to assess mavorixafor’s long-term safety and durability (NCT04154488). On September 27, X4 Pharma announced the 25-patient Phase Ib trial would expand to include 25 additional patients, with initial data expected in H1 2023. In topline data from the initial 25 patients, all patients treated with mavorixafor achieved a treatment response of increased neutrophil levels.

“The Phase Ib data shows mavorixafor can tap into bone marrow reserves and enable neutrophils to move out and fight infections,” Ragan says. “Now the expansion will answer the question: is the response durable?”

Meanwhile, X4 Pharma has an ongoing 28-patient Phase III trial (NCT03995108) in WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis)—a rare immune deficiency that can cause neutropenia. Results from the trial are expected in Q4, with an open-label extension to follow, Ragan adds.

Drug trials in neutropenia

While there has been steady growth among Phase I trials for drugs sponsors intend to test in neutropenia, the number of later-stage trials initiated has slowed down, according to GlobalData’s Clinical Trials Database. GlobalData is the parent company of Clinical Trials Arena.

Phase I trials for drugs in neutropenia accounted for 2.4% of hematological disorder drug trials initiated in 2022, up from 0.2% in 2013. Meanwhile, Phase II and Phase III drug trials accounted for 1.2% of such trials in 2022, down from 2.5% in 2013.

Drug trials in hematological disorders had among the highest proportion of disruptions in Covid-19, possibly contributing to the recent downturn in Phase II and Phase III studies. Meanwhile, the Asia-Pacific region has seen the highest level of recent growth in such trials.