Third time unlucky: Lipocine's latest quest to market their oral testosterone drug snubbed again by FDA
Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.
The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.
Shares of the Salt Lake City company $LPCN cratered more than 69% to 84 cents in morning trading.
Testosterone treatments such as skin patches, short-acting injections, and topical gels are currently on the market. The space is well covered by insurers and is growing, generating some 7.2 million prescriptions last year, according to Cowen analysts. But their popularity in the aging male demographic has become a problem for some biotechs in the field, with regulators rejecting a number of applications in recent years.
Intramuscular injections are often the first-line testosterone replacement therapy (TRT) modality due to the fact that they have long been generic, before graduating to the branded topical products (or even the generic topicals, which carry only modest discounts to branded AndroGel), the Cowen analysts wrote in April. “The topical products such as AbbVie’s AndroGel and Lilly’s Axiron appear to be readily accessed, despite their branded/branded generic pricing.”
Tlando is designed to avert the issues that plague the existing topical and injectable products. Lipocine’s big rival, Clarus Therapeutics, in March, won FDA approval for its oral product, Jatenzo. Lipocine and Clarus have been locked in litigation related to intellectual property associated with their respective therapies.
Months ago, Lipocine said a trial is set to begin in August 2020 as part of its patent infringement lawsuit against Clarus’s Jatenzo, relating to six of Lipocine’s U.S. patents. In the meantime, Lipocine plans to seek a permanent injunction for Clarus’s alleged infringement.
Lipocine has been scarred time and time again in its battle to bring Tlando to market. The company received its first rejection from the FDA in 2016, about a year after the agency tightened its scrutiny of TRT products in general. The regulator in March 2015 asked manufacturers to tweak their labels to reflect that TRT products are only approved for men with certain medical conditions, and not for aging-related low testosterone; and that data suggest TRT use leads to an increased risk of heart attacks and strokes.
In 2016, the agency indicated it was not comfortable with the Tlando dosing algorithm. “The proposed titration scheme for clinical practice was significantly different from the titration scheme used in the Phase 3 trial leading to discordance in titration decisions between the Phase 3 trial and real-world clinical practice,” Lipocine cited the FDA saying in a statement.
Lipocine resubmitted a marketing application in 2017. In an FDA staff review that followed in 2018, the agency said it had recommended that the company conduct a new Phase III trial that tests the dose titration scheme proposed for marketing. Instead, Lipocine chose to conduct two new single-arm late-stage trials, each testing a different dose of Tlando (150 mg thrice-daily and 225 mg twice-daily) without titration. The 150 mg trial failed, but the 225 mg dose made the cut.
FDA panelists also expressed other concerns, including that the original late-stage trial upon which Lipocine had based its application on did not meet one or none of the three secondary endpoints that assess for unacceptably high maximal exposures to testosterone; the drug’s impact on the patient’s blood pressure and heart rate; and whether Tlando was definitely restoring testosterone and its major metabolites into normal range.
Days later, an independent panel of advisors to the FDA also suggested their discomfort with the drug. Overall, thirteen panelists voted against the benefit/risk profile of Tlando, while six voted in favor. Unsurprisingly, the FDA handed Lipocine another rejection.
So Lipocine conducted another study, a small 24-patient trial to definitively show that the drug was definitively restoring testosterone levels, using trial protocol the FDA was looking for. But on Monday, the FDA’s CRL flagged a problem the company had failed to deal with from the start: that the original efficacy trial failed to show the drug clearing three secondary endpoints for maximal testosterone concentrations.
The company plans to meet with the agency to figure out its next steps.