Rare Daily Staff

The U.S. Food and Drug Administration granted X4 Pharmaceuticals Breakthrough Therapy Designation for mavorixafor for the treatment of adult patients with the rare genetic syndrome WHIM.

Breakthrough Therapy Designation is granted by the FDA to investigational medicines intended to treat a serious or life-threatening condition for which preliminary clinical evidence may demonstrate substantial improvement on at least one clinically significant endpoint over available therapy. It is intended to expedite development and review.

WHIM syndrome is a rare, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. It is named for the characteristic clinical symptoms of the syndrome – Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Patients with WHIM may experience significant morbidity beginning in early childhood and continuing throughout life with an increased likelihood of various recurrent, potentially life-threatening infections, and may also be susceptible to malignancies such as HPV-related cervical cancer and lymphomas. The overall cancer risk in patients with WHIM is estimated to be 30 percent by 40 years of age. There are no approved therapies for WHIM. Although the exact prevalence of WHIM is unknown, in the United States there are between 15,000 and 100,000 patients classified as having a primary immunodeficiency disease of unknown origin – of which WHIM is one.

Mavorixafor is a potential first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4, and is currently being investigated in a pivotal phase 3 global clinical trial for the treatment of WHIM syndrome.

The Breakthrough Therapy designation granted to mavorixafor is based on data from X4’s phase 2 open-label, multi-center trial of mavorixafor in adult patients with WHIM syndrome. In this trial, proof of concept was established based on clinically meaningful increases in absolute neutrophil counts, absolute lymphocyte counts, evidence indicating reductions in infection rates and wart burden, and a safety profile showing that mavorixafor is well-tolerated.

“Rare diseases such as WHIM don’t often receive the attention and research patients and their families deserve. The FDA’s decision to grant Breakthrough Therapy Designation to mavorixafor for the treatment of adults with WHIM syndrome represents a significant milestone for patients and X4 alike, helping to further highlight the severity of this underdiagnosed disease and the importance of offering a potential novel, disease-modifying therapeutic option to this underserved patient population,” said Paula Ragan, president and CEO of X4 Pharmaceuticals.

Mavorixafor was granted orphan drug status by the FDA in 2018 and by the European Commission in 2019 for the treatment of WHIM syndrome. X4 is also developing the drug for the treatment of severe congenital neutropenia, Waldenström’s macroglobulinemia, and clear cell renal cell carcinoma.

Photo: Paula Ragan, president and CEO of X4 Pharmaceuticals

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