X4 Pharmaceuticals gains FDA approval for WHIM syndrome drug XOLREMDI

The U.S. Food and Drug Administration (FDA) has approved X4 Pharmaceuticals’ XOLREMDI (mavorixafor) capsules for use in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.

XOLREMDI, a selective CXC chemokine receptor 4 (CXCR4) antagonist, is the first therapy specifically indicated in patients with WHIM syndrome, a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 pathway dysfunction. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia) and experience serious and/or frequent infections.

The FDA granted Breakthrough Therapy Designation to mavorixafor in WHIM syndrome and evaluated the New Drug Application (NDA) under Priority Review, a designation for therapies that have the potential to provide significant improvement in the treatment, diagnosis, or prevention of serious conditions.

“The approval of XOLREMDI is a transformational milestone both for X4 and, more importantly, for the WHIM syndrome community,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “We are incredibly grateful to the people living with WHIM syndrome, their families, and the investigators who took part in our clinical program, to U.S. regulators for their continued focus on rare-disease treatment development, and to our dedicated employees for making this targeted breakthrough therapy a reality.”

The FDA approval of XOLREMDI was based on results of the pivotal, 4WHIM Phase 3 clinical trial, a global, randomized, double-blind, placebo-controlled, 52-week multicenter study that evaluated the efficacy and safety of XOLREMDI in 31 people aged 12 years and older diagnosed with WHIM syndrome. The efficacy of XOLREMDI was determined by improvement in absolute neutrophil counts (ANC), improvement in absolute lymphocyte counts (ALC), and a reduction in infections.

In the 4WHIM trial, XOLREMDI treatment demonstrated increased time above threshold (≥500 cells/microliter) for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001) and increased time above threshold (≥1000 cells/microliter) for absolute lymphocyte count (TAT-ALC) v. placebo (p<0.0001). The efficacy of XOLREMDI was further assessed in a composite endpoint consisting of total infection score and total wart change score using a Win-Ratio method.

Analyses of the individual components of this composite endpoint showed an approximate 40% reduction in total infection score, weighted by infection severity, in XOLREMDI-treated patients compared with placebo-treated patients. There was no difference in total wart change scores between the XOLREMDI and placebo treatment arms over the 52-week period.

Treatment with XOLREMDI also resulted in a 60% reduction in the annualized infection rate compared with placebo-treated patients. The most common adverse reactions reported in the 4WHIM trial (≥10% and more frequently reported than placebo) were: thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.

With the FDA approval of XOLREMDI, X4 has received a Rare Pediatric Disease Priority Review Voucher that can be used to obtain priority review for a subsequent application or sold to another drug sponsor.

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