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The indication is for patients aged 12 years of age and older, and the treatment is intended to increase the number of mature neutrophils and lymphocytes in patients.
The FDA has approved mavorixafor capsules (Xolremdi; X4 Pharmaceuticals) for the treatment of patients 12 years of age and older who have warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM syndrome) to increase the number of circulating mature neutrophils and lymphocytes. The approval follows results from the phase 3 clinical trial, 4WHIM (NCT03995108).1
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Mavorixafor is a selective CXC chemokine receptor 4 (CXCR4) antagonist and is the first therapy specifically indicated to treat patients with WHIM syndrome. Previously, mavorixafor received a breakthrough therapy designation and was evaluated under priority review by the FDA. WHIM syndrome is a chronic neutropenic disorder caused by a CXCR4 pathway dysfunction, and those who have WHIM syndrome experience low levels of neutrophils and lymphocytes in the blood while having serious and/or frequent infections.1
“Effective and innovative treatments are critical for those diagnosed with a primary immunodeficiency. The approval of [mavorixafor] marks an important advancement for people living with WHIM syndrome, who are susceptible to serious and frequent infections,” said Jorey Berry, president and CEO of the Immune Deficiency Foundation (IDF), in a press release. “We are very pleased to have been a partner to X4 in their journey to bring this much-needed treatment to this underserved rare disease community.”1
Trial Name: Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
ClinicalTrials.gov ID: NCT03995108
Sponsor: X4 Pharmaceuticals
Completion Date (Estimated): December 2024
The global, multicenter, randomized, double-blind, placebo-controlled 4WHIM study evaluated the safety and efficacy of mavorixafor in patients aged 12 years and older who have WHIM syndrome. A total of 31 patients were randomly assigned to receive 400 mg or 200 mg of oral, once-daily mavorixafor depending on weight (400 mg: >50 kg; 200 mg: ≤50 kg), or placebo. Patients were observed over a 52-week period.1,2
The primary end point of the trial was time above absolute neutrophil counts (ANC) threshold (≥500/μL). Secondary end points included time above threshold (TAT) ANC (≥1000/μL); absolute changes in white blood cell, ANC, and absolute lymphocyte counts (ALC) from baseline; annualized infection rates; and infection duration, as well as its total score.3
Among the 31 patients enrolled, 14 received mavorixafor and 17 received placebo. According to the findings, treatment with mavorixafor resulted in lower infection frequency, severity, duration, and antibiotic use. The mavorixafor group experienced an approximate 40% reduction in total infection score (7.4 [95% CI, 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]) and infection rates were about 60% lower compared with placebo (LS mean 1.7 vs 4.2; nominal P = 0.007). The investigators note that mavorixafor was well-tolerated in patients.1,3
“Until now, supportive care for people with WHIM syndrome has focused on symptom management and not the underlying cause of disease—the dysfunction of the CXCR4 pathway. I am thrilled that with the approval of [mavorixafor], a therapy designed to address dysregulated CXCR4 pathway signaling, we now have a targeted treatment that has demonstrated the ability to elevate ANC and ALC, increasing [the] ability [of patients with WHIM] to fight infections,” said principal trial investigator Teresa K. Tarrant, MD, associate professor of medicine, rheumatology, and immunology at Duke University School of Medicine, in the press release.1
The most common adverse events (AEs) reported by patients during the trial were thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness. Additionally, the investigators noted that there were no treatment discontinuations that were a result of treatment-emergent AEs, and no serious occurrences of treatment-emergent AEs were observed.1,3
“The approval of [mavorixafor] is a transformational milestone both for X4 and, more importantly, for the WHIM syndrome community,” said Paula Ragan, PhD, president and CEO 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 US regulators for their continued focus on rare-disease treatment development, and to our dedicated employees for making this targeted breakthrough therapy a reality.”1
