An FDA advisory committee has declined to recommend approval of a proposed new oral testosterone replacement therapy (Tlando, Lipocine Inc.).
Lipocine said the Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) voted six in favor and 13 against the benefit–risk profile of Tlando, which is aimed at adult males for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism. The role of BRUDAC is to provide recommendations to the FDA. The FDA decision on whether or not to approve the Tlando new drug application (NDA) is anticipated by the assigned Prescription Drug User Fee Act goal date of May 8, 2018.
According to a report from Fierce Biotech, the drug has been dogged by questions about cardiovascular adverse events and an effect on blood pressure. Those concerns date back to data Lipocine generated to support its first NDA for approval of Tlando. A 52-week trial run before the 2015 filing tracked a rise in the heart rates of patients who received Tlando and the active comparator topical AndroGel. That trial also reported a decline in high-density lipoprotein-cholesterol levels in close to half of participants in the Tlando arm.
"We continue to believe that efficacy and safety results from numerous clinical studies with Tlando are consistent with other FDA-approved TRT products," said Dr. Mahesh Patel, Chairman, President, and Chief Executive Officer of Lipocine. "We look forward to continuing to work with the FDA through the remainder of the review process."
The NDA under review by the FDA includes efficacy and safety data from three phase 3 clinical trials: the Dosing Validation (DV) clinical study, the Dosing Flexibility clinical study, and the Study of Oral Androgen Replacement (SOAR) clinical study. Lipocine resubmitted the NDA to the FDA in August 2017 based on the results of the DV study. The DV study confirmed the efficacy of Tlando with a fixed dose regimen without the need for dose adjustment. Tlando met the FDA primary efficacy guidelines in the DV study safety statistical analysis set, where 80% of the subjects achieved average testosterone levels within the normal range with a lower bound confidence interval of 72%. Tlando was well tolerated upon 52-week exposure with no reports of drug related serious adverse events.