X4 Pharmaceuticals, Inc. announced positive new clinical data from its ongoing Phase 2 clinical trial evaluating the safety and efficacy of mavorixafor, an oral CXCR4 antagonist, in the treatment of people with chronic neutropenia (CN). An interim analysis of data from the ongoing six-month study showed that once-daily oral mavorixafor was generally well tolerated and durably increased participants? absolute neutrophil counts (ANC) both as a monotherapy and in combination with stable doses of injectable granulocyte colony-stimulating factor (G-CSF), the only therapy approved in the U.S. for severe chronic neutropenia.

The company also announced that it is currently screening patients for enrollment into its global, pivotal Phase 3 clinical trial, the 4WARD study, evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without stable doses of G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic CN who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants. The Phase 2 study of mavorixafor is a six-month, open-label clinical trial that enrolled a total of 23 participants diagnosed with idiopathic, congenital, or cyclic CN.

The interim analysis included results from the two treatment groups in the study (mavorixafor monotherapy and mavorixafor with stable-dose G-CSF) that most closely mirror the participant population of the newly initiated Phase 3 4WARD trial. Fifteen participants were enrolled across these two groups and, as of the May 14, 2024 interim analysis data cut-off date, seven had completed the study, and five remain ongoing. Data from a third treatment group of eight participants receiving mavorixafor and dose-adjusted G-CSF are expected to be presented later this year.

The mavorixafor monotherapy group included 10 participants and the mavorixafor with stable-dose G-CSF group included five participants. As of the data cut-off date, findings from the interim analysis show: 100% (6/6) of evaluable participants who had completed the six-month study achieved target ANC increase (ANC >500 cells/µL) at Months 3 and 6 on once-daily mavorixafor therapy with or without stable-dose G-CSF. Participants on mavorixafor monotherapy achieved mean ANC levels above the lower limit of normal for CN (=1,500 cells/µL) at Month 3 (n=8) and Month 6 (n=3).

Mavorixafor monotherapy also durably increased ANC in participants with severe CN (ANC<500 cells/µL at baseline), achieving mean ANC of ~800-1,000 cells/µL (ANC range targeted by experts) at Months 1, 3, and 6 (n=5, 3, and 2, respectively). Participants on mavorixafor in combination with stable-dose G-CSF experienced increases in mean ANC of >1,000 cells/µL at Months 1, 3, and 6 (n=4, 4, and 3, respectively) versus baseline. Across the 23 participants enrolled in the study, mavorixafor was generally well tolerated as a monotherapy and in combination with G-CSF, with no drug-related serious adverse events reported, as of the interim analysis data cut-off date.

Of the 23 participants, three discontinued due to non-serious adverse events. The overall safety profile remains consistent with previous clinical studies. The Phase 1b/Phase 2 clinical trial (NCT04154488) is a proof-of-concept, open-label, multicenter study designed to assess the safety and tolerability of oral mavorixafor, with or without injectable G-CSF, in participants with chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenia.

In the Phase 1b portion of the study, participants received one dose of oral mavorixafor and were assessed for magnitude of absolute neutrophil count (ANC) response and tolerability. In this initial portion of the study, 100% of participants (n=25) responded to treatment and mavorixafor was generally well tolerated alone or dosed concurrently with G-CSF. The ongoing Phase 2 portion of the trial (n=23 fully enrolled) is assessing the safety, tolerability, and the impact on participants?

neutropenia of oral, once-daily mavorixafor with and without concurrent injectable G-CSF therapy over a six-month period.