Lipocine Receives FDA Complete Response Letter for Testosterone Therapy Candidate

The US Food and Drug Administration (FDA) has submitted a Complete Response Letter (CRL) to an applicant specialty pharmaceutical company that is trying to push an oral testosterone product to the market.

Salt Lake City-based company Lipocine has announced it received a CRL from the FDA in response to its New Drug Application (NDA) for testosterone replace therapy (TRT) candidate TLANDO. The treatment has been investigated for the treatment of adult men with deficiencies of endogenous testosterone.

The CRL detailed 4 found deficiencies in the Lipocine product, including the following:

• Lack of reliable T data in determining any extent of ex vivo conversion of testosterone undecanoate (TU) to testosterone via serum blood collection tubes
• Failure to obtain definite evidence pre-approval via an ambulatory blood pressure monitoring study as to whether TLANDO causes a clinically meaningful increase in blood pressure in hypogonadal men
• Verifying the reliability of Cmax data and providing justification for non-applicability of the agree-upon Cmax secondary endpoints for the therapy
• Determining the appropriate stopping criteria that can reproducibly and accurately identify those patients who should discontinue use of the therapy

Other issues addressed in the CRL are not considered approvability-dependent. Lipocine intends to meet with the FDA to further evaluate these noted deficiencies and seek progress towards approval of TLANDO for its proposed indication.

According to documents provided by an FDA subcommittee that gauged the investigative therapy in January, Lipocine — on its second application for TLANDO — had conducted 2 new single-arm phase 3 trials that tested a single dose of the therapy without titration over 24 days.

The trials, testing 150 mg TLADNO orally 3 times daily and 225 mg orally twice daily in patients, were considered sufficient duration periods due to there being no dose adjustment and previous data that indicated the therapy reaches steady-state following 14 days of treatment.

The company also provided 1-plus year of safety for 193 patients treated with TLANDO — 131 of whom were on a dose of at least twice-daily 225 mg by the end of trials.

Mahesh Patel, MD, chairman, president and chief executive officer of Lipocine, did not express surprise at the FDA decision, but has hope for the therapy moving forward.

“While we are disappointed by the FDA's decision, the deficiencies identified in the CRL are within our expectations following the meeting we had on January 10, 2018 with the Bone, Reproductive and Urologic Drugs Advisory Committee of the FDA,” Patel said. “We are assessing the content of the CRL, including the information that may be needed to resolve the deficiencies. We remain committed to work with the FDA to bring TLANDO to patients.”