Xeris Biopharma Reports Positive Phase 2 Results for Once-Weekly SC Levothyroxine (XP-8121)

Xeris Biopharma, Inc., a forward-looking biopharmaceutical company, recently shared promising results from its Phase 2 study on XP-8121, a groundbreaking once-weekly subcutaneous (SC) formulation of levothyroxine for treating hypothyroidism. Utilizing the company’s XeriSol™ technology, this novel formulation significantly enhances levothyroxine's bioavailability, offering a solution to the challenges associated with daily oral treatments.

The Phase 2 study was an open-label, single-arm investigation involving 46 hypothyroid patients. Participants transitioned from stable daily oral doses of levothyroxine to once-weekly SC injections of XP-8121. The study confirmed that XP-8121 delivered predictable bioavailability and maintained consistent thyroid-stimulating hormone (TSH) and T4 levels with 45% less drug than the weekly equivalent of their daily oral doses.

During the study, participants initially started with an XP-8121 dose equivalent to twice their daily oral dose, titrating up to a target of four times their daily dose. By the maintenance period, the average weekly dose administered was approximately 324.4 mcg. Remarkably, the geometric mean conversion factor from daily to weekly dosing was found to be 4.02, corroborating findings from a prior Phase 1 study.

Despite the shift in administration route, XP-8121 was well-tolerated. About 65.2% of participants reported at least one treatment-emergent adverse event (TEAE), predominantly mild to moderate in severity, including fatigue, injection site pain, headache, and urinary tract infections. Importantly, no serious adverse events or deaths were reported, and no participants withdrew from the study due to injection site reactions.

Patient satisfaction was significantly higher with XP-8121 compared to daily oral levothyroxine. Utilizing the Treatment Satisfaction Questionnaire for Medication (TSQM-9), XP-8121 scored better across effectiveness, convenience, and overall satisfaction. Furthermore, 72% of participants expressed a strong preference for the SC route due to its convenience and ease of administration.

The study's findings highlight the challenges of maintaining stable TSH levels with daily oral levothyroxine, a problem underscored by the discovery that 40% of patients deemed stable at screening had abnormal TSH or T4 levels. Given these challenges, XP-8121 presents a viable alternative that could enhance patient compliance and therapeutic outcomes.

The study's success paves the way for a pivotal Phase 3 trial, with an FDA End-of-Phase 2 meeting anticipated by the end of the year. The potential of XP-8121 to address a significant unmet need in hypothyroidism management is notable, considering the high prevalence of the condition in the U.S., affecting approximately 11.7% or 30 million adults.

Hypothyroidism, characterized by insufficient thyroid hormone production, affects various bodily functions, including metabolism, heart rate, and mood. Levothyroxine, a synthetic form of the thyroid hormone, is the standard treatment, typically requiring lifelong administration.

Xeris' XeriSol™ technology, integral to XP-8121, offers a non-aqueous formulation that enhances the stability and solubility of drugs, allowing for room temperature-stable, ready-to-use formulations. This technology has been successfully applied in other commercial products and clinical trials, underlining its robustness.

Xeris Biopharma, headquartered in Chicago, continues to innovate in the biopharmaceutical sector with a portfolio that includes products like Gvoke® for severe hypoglycemia, Keveyis® for primary periodic paralysis, and Recorlev® for Cushing’s syndrome. The company's ongoing development efforts, supported by proprietary technologies like XeriSol™ and XeriJect®, exemplify its commitment to improving patient outcomes across various therapeutic areas.