Four months after implementing a restructuring initiative to extend cash flow, X4 Pharmaceuticals is celebrating positive top-line results in WHIM syndrome.
Paula Ragan, X4 President and CEO/company courtesy
Four months after implementing a restructuring initiative to extend cash flow, X4 Pharmaceuticals is celebrating positive top-line results, released Tuesday, from its pivotal Phase III trial of mavorixafor in WHIM syndrome.
In July, the Boston-based biopharma made the tough call to cut its workforce by 20% and discontinue its oncology programs, leaving these to only advance via a partnership.
These changes were expected to save the company $5 million this year and $20 million in 2023. Coupled with a $55 million capital raise, X4 expected to be able to extend its cash runway into Q3, 2023 as it held out for a Phase III readout.
That moment arrived when X4 revealed results from its lead investigational therapy, mavorixafor. The CXCR4 antagonist was tested against placebo in 31 patients 12 years and older with WHIM syndrome.
WHIM is a rare, congenital immune deficiency named for its four main characteristics – warts, hypogammaglobulinemia, infections and myelokathexis. Patients are particularly susceptible to infection and developing certain types of cancers due to low neutrophil and lymphocyte counts.
Currently, there are no ongoing treatments available to WHIM patients. Some receive immunoglobulin replacement therapy to boost IgG antibody levels. If infections become severe, patients may receive G-CSF, a type of growth factor that boosts white blood cell production.
“[These current] medicines require injections and needles,” Dr. Teresa Tarrant, associate professor of medicine at Duke specializing in immunology and principal investigator in the 4WHIM trial, told BioSpace.
“[Mavorixafor] is an oral medicine. That makes this a very exciting therapeutic. It is molecular medicine at its best. Patients have defects in the CXCR4 protein and this treatment addresses that directly. Personalized therapy moving forward for patients with rare diseases is something we’re really excited about.”
Mavorixafor was well tolerated in the trial and achieved both primary and secondary endpoints to raise patient neutrophil and lymphocyte counts above clinically meaningful thresholds.
After the trial’s completion, 90% of placebo recipients opted to receive the treatment in an open-label trial extension.
Mavorixafor works by blocking the hyperactivated signaling by CXCR4, the cell receptor for CXCL12, to regulate the release of immune cells from the bone marrow into the peripheral blood. X4 believes inhibiting the CXCR4/CXCL12 axis could improve immune deficiencies whether caused by a CXCR4 mutation or not.
If approved, mavorixafor would be the first therapy to treat the underlying cause of WHIM syndrome. X4 is prepping to meet with regulatory authorities in the first half of 2023 to get the drug on the path to approval and commercialization, interim Chief Medical Officer Murray Stewart said in a press release.
While WHIM is considered extremely rare, part of the low number of diagnoses could be due to a lack of universal genetic testing and limited awareness of the disease.
To combat this, X4 has partnered with Invitae to launch no-cost genetic testing for people who may carry genetic mutations associated with chronic neutropenia to assist with better diagnostics.
The therapy is also believed to be useful for a variety of chronic neutropenic disorders, as the CXCR4 pathway is a key regulator of neutrophil release from bone marrow. Mavorixafor is currently being studied in a Phase Ib trial for these patients both as a monotherapy and in combination with the standard of care, G-CSF.
“These results that have been released today are extremely promising and exciting for the potential to look into other diseases where low neutrophil counts cause problems for people,” Tarrant said.
“It’s very, very encouraging. I think we all are hopeful for an even broader impact.”
X4 has a second CXCR2 antagonist in preclinical development, but the program is currently on hold and depends on mavorixafor’s approval to be advanced.
