Xeris Biopharma has the green light to take its subcutaneous levothyroxine into phase 2. After talking to the FDA, the company outlined plans to start a midphase trial of the investigational alternative to oral hypothyroidism therapy in the second half of next year.
Chicago-based Xeris applied its formulation technology to levothyroxine in light of evidence of the issues patients face when taking the thyroid hormone replacement therapy orally. According to Xeris, “the complexity of maintaining biochemical and clinical euthyroidism in patients undergoing treatment with oral levothyroxine cannot be underestimated.”
The company quoted evidence that nearly 40% of patients are either over- or under-treated because of factors related to formulation, use of the drug with food, adherence, use of concomitant medications and preexisting conditions. Many patients fail to reach target hormone levels. Increasing the dose can “cause a clinically meaningful shift in pharmacological effects” because of the narrow therapeutic index.
Xeris generated evidence that its subcutaneous formulation, XP-8121, may overcome some of the issues of oral levothyroxine earlier this year when it reported top-line data from a phase 1 clinical trial. The trial linked XP-8121 to slower absorption, lower peak plasma and higher extended exposure than AbbVie’s oral levothyroxine product Synthroid PO at a comparable dose. The results have teed up further trials.
“We received very productive feedback from the FDA on our proposed clinical plan for our once weekly subcutaneous levothyroxine and are in the process of clarifying some aspects of the phase 2 and phase 3 recommendations. We believe we have enough clarity to move forward with a phase 2 study, which we anticipate having up and running by the second half of 2023,” Paul Edick, Xeris’ chairman and CEO, said in a statement.
The phase 2 trial will be a dose-finding study. Xeris sees the study establishing the average once-weekly dose and generating chronic safety data to support a planned phase 3 program.