Lipocine Inc. announced positive topline study results demonstrating bioequivalence of LPCN 1154 to IV brexanolone in an NDA enabling pivotal pharmacokinetic (PK) study. Lipocine is developing LPCN 1154, oral brexanolone, for the treatment of postpartum depression (PPD). The U.S. Food & Drug Administration (FDA) has agreed with Lipocine's proposal for a 505(b)(2) NDA filing based on a single pivotal PK bridging study comparing exposure of LPCN 1154 with the approved IV infusion of brexanolone.

Intravenous brexanolone is approved based on evidence demonstrating efficacy and safety with two dosing regimens with different maximum infusion rates of either 60 µg/kg/hr (IV60) or 90 µg/kg/hr (IV90). Lipocine is targeting NDA submission by the end of the fourth quarter of 2024. Per published FDA bioequivalence guidance1, the criteria to establish bioequivalence are that Geometric Mean Ratios (GMR) and corresponding 90% confidence intervals (CIs) for AUC0-t, AUC0-8, and Cmax (key measures of drug exposure) fall within 80% to 125% for test vs reference products.

The pivotal PK study was an open label, randomized, crossover study in 24 healthy postmenopausal women utilizing the "to be marketed" formulation and oral dosing regimen of LPCN 1154 and the commercial IV brexanolone formulation using the approved high dose infusion regimen (IV90). The primary objective of the study is to compare the PK of a multi-dose regimen of oral LPCN 1154 (test product) to IV infusion brexanolone (reference product). Twenty-four post-menopausal women were randomized (safety set), and all completed dosing in both study periods.

The PK analysis data set includes 23 participants; data from one participant meeting outlier criteria was excluded. LPCN 1154 and IV90 brexanolone were bioequivalent based on GMRs and 90% CIs for Cmax, AUC0-8, and AUC0-t meeting established criteria. As targeted, Ctrough of LPCN 1154 geometric mean was higher than the trough of IV brexanolone (geometric lower 90% CI).

LPCN 1154 treatment was well tolerated with no sedation nor somnolence events observed. All events were mild to moderate, and no severe or serious adverse events occurred. Reported study related events were venipuncture site reaction, headache, arthralgia, fatigue, dizziness, low back pain, and pelvic pain and no event was reported by more than two participants.

PPD is a major depressive disorder with onset either during pregnancy or within four weeks of delivery, with symptoms persisting for up to 12 months after childbirth. There is an unmet need for an oral fast-acting product with an improved efficacy and safety profile to treat PPD. Oral LPCN 1154 comprising a bioidentical neuroactive steroid is designed to provide rapid relief with robust efficacy and 48-hour outpatient dosing.

Recent reports suggest that the market size for PPD is larger than previously estimated. Approximately 500,000 women are affected by PPD annually in the United States and, according to the CDC, an estimated 175,000 women suffer from moderate to severe PPD. Increasing awareness of PPD among physicians and patients is expected to result in higher diagnosis rates and greater numbers of patients seeking treatment.