FDA Approves First Targeted Treatment for WHIM Syndrome


Pictured: X4 CEO Paula Ragan/courtesy X4 Pharmaceuticals.

The FDA has approved X4 Pharmaceuticals’ Xolremdi as the first targeted treatment for the ultra-rare immunodeficiency disease WHIM syndrome.

According to the NIH, fewer than 1,000 people in the U.S. have been diagnosed with WHIM, which is an acronym for the four characteristics of the disease—warts, hypogammaglobulinemia, infections and myelokathexis. Hypogammaglobulinemia is a disorder caused by low antibody levels, while myelokathexis is a congential disorder of the white blood cells.

Xolremdi (mavorixafor) is an oral CXCR4 antagonist designed to mobilize white blood cells such as neutrophils, lymphocytes and monocytes from the bone marrow into the blood to improve immune deficiencies. It is approved for patients 12 and older.

Xolremdi is X4’s first marketed drug, and CEO Paula Ragan told BioSpace that going commercial is a “big step.” The company is putting together a “field force” to educate and raise awareness of and sell the drug, Ragan said.

“I think that’s a really important moment for any company; it’s really showing the lifelong commitment that we’re making to being here in perpetuity,” she continued. “It’s a privilege to gain an FDA approval of a drug, and I believe in rare disease, it’s a responsibility to keep investing and being there for the patients as they need us.”

In May 2023, X4 reported positive Phase III results from the 4WHIM trial of Xolremdi showing a 60% reduction in annualized infection rate compared to placebo; trial participants had less than one infection per year compared with 4.5 for the placebo group. Patients also saw a greater reduction with more time on treatment.

Teresa Tarrant, an associate professor at Duke University’s School of Medicine and lead investigator of the 4WHIM trial, told BioSpace that current treatments for the disease are only supportive and gave the example of prescribing Gardasil to treat warts. Prior to Xolremdi’s approval, there was not an easy way to treat WHIM’s underlying symptoms, she said.

“I think that for a lot of patients, the idea that there is a targeted therapy . . . something that is directly correcting the underlying problem for the individual, I think that gives them a lot of hope, a lot of optimism,” Tarrant said. “It’s an exciting time for personalized medicine, and I think WHIM is going to be a poster child for rare diseases and the ability where we’re at now in modern medicine to design therapies to treat underlying genetic disorders.”

Ragan echoed this sentiment, saying, “I think what we are excited about mostly is the fact that with all of these ultra-orphan disease settings, the ideal objective is to show a targeted treatment really impacting the broad symptoms of the disease.”

X4’s victory Monday has not been without its challenges. In July 2022, the company cut around 20% of its workforce and stopped work on its oncology programs.

Ragan said X4 now plans to grow the commercialization end of its business and is close to filling out that department. The company plans to be ready on “day one post-approval,” she said.

X4 has set the price for Xolremdi at around $496,000 per year for patients weighing more than 50 kilograms, and about $372,000 for patients weighing less than or equal to 50 kilograms, according to a company spokesperson.

With the approval, X4 received a Rare Pediatric Disease priority review voucher, which Ragan said on a conference call the company plans to monetize.

Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

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