Xeris Biopharma Holdings, Inc. announced topline results from its recently completed Phase 2 multi-center, open label, study of XP-8121 for the treatment of adults with hypothyroidism. XP-8121 employs the Company?s XeriSol? formulation technology to enable a novel once-weekly SC injection of levothyroxine.

This novel formulation significantly increases the bioavailability of levothyroxine reducing overall drug exposure and enabling a dosing regimen with the potential to mitigate the many challenges associated with achieving and maintaining a normal level of thyroid stimulating hormone (TSH) with daily oral formulations of levothyroxine. The Phase 2 study (NCT05823012) was a non-randomized, open-label, single arm, self-controlled study of XP-8121 (levothyroxine sodium) to determine a target dose conversion factor from stably dosed oral levothyroxine to XP-8121 (levothyroxine sodium) in 46 patients with hypothyroidism and to assess the safety and tolerability of XP-8121 (levothyroxine sodium) after once-weekly SC injections. The Phase 2 study leveraged the bioavailability observations of a previous Phase 1 study in which PK analysis showed that participants could achieve comparable systemic exposure with XP-8121 at only 57% of a weekly oral dose.

The Phase 2 study included the following periods: Screening, Titration Period (2 to 8 weeks), and Maintenance Period (4 weeks). Participants entered the study on a stable oral dose (= 3 months) with normal TSH and free T4 laboratory values. Participants were receiving a daily oral levothyroxine dose of 83.7 ± 31.14 mcg (mean ± SD) at study entry.

To ensure the safety of study participants, once-weekly SC injection of XP-8121 was initiated at 2X their daily dose and titrated every 2 weeks to a target of 4X their daily dose. Participants completing the Maintenance Period were receiving a weekly XP-8121 dose of 324.4 ± 125.59 mcg. The geometric mean ratio of the once-weekly dose of XP-8121 to the daily dose levothyroxine (aka dose conversion factor) was 4.02 [90% CI 3.79, 4.27].

A total of 30 participants (65.2%) experienced at least 1 TEAE (Treatment Emergent Adverse Event) with most rated mild (87%) and moderate (13%) in severity. The most frequent (> 2 participants) TEAE included fatigue (21.7%), injection site pain (10.9%), headache (8.7%) and urinary tract infection (6.5%). No deaths or other serious adverse events (SAEs) were reported.

Injection site tolerability was assessed with every SC administration of XP-8121 (> 450 injections). There were very few reports of discomfort (18%; mostly mild intensity), erythema (7%; Draize scale) or edema (1%; Draize scale). No participant discontinued from the study due to an injection site reaction.

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) was administered to assess patient satisfaction. XP-8121 scored consistently higher in all three domains (effectiveness, convenience, and global satisfaction) compared to oral levothyroxine. At the conclusion of the study, participants were asked to rate preference for once-weekly XP-8121.

A majority (72%) indicated a strong preference for the SC route of administration based on categorical attributes of convenience (60.6%), ease of administration (45.5%), frequency of administration (54.5%), level of compliance (27.3%) and confidence in therapy (36.4%).