Lipocine: LPCN 1154 Bioequivalent to IV Brexanolone in Key Study

Lipocine Inc., a biopharmaceutical company specializing in enhancing therapeutics through effective oral delivery, announced promising topline results from a pivotal pharmacokinetic (PK) study demonstrating bioequivalence of LPCN 1154 to intravenous (IV) brexanolone. LPCN 1154 is being developed as an oral treatment for postpartum depression (PPD). The U.S. Food & Drug Administration (FDA) has agreed with Lipocine's proposal for a 505(b)(2) New Drug Application (NDA) filing, which is anticipated by the end of the fourth quarter of 2024.

Dr. Mahesh Patel, President and CEO of Lipocine, expressed satisfaction with the study results, highlighting the potential of LPCN 1154 to offer a new oral treatment option for PPD patients. PPD is a serious and potentially life-threatening condition, and LPCN 1154 aims to be an effective, fast-acting oral treatment with a short duration of just 48 hours.

The FDA's bioequivalence criteria necessitate that the Geometric Mean Ratios (GMR) and 90% confidence intervals (CIs) for various pharmacokinetic measures like AUC0-t, AUC0-∞, and Cmax fall between 80% to 125% when comparing test and reference products. The pivotal study was an open-label, randomized, crossover study involving 24 healthy postmenopausal women. It compared the PK of LPCN 1154 (oral) with the commercial IV formulation of brexanolone.

Twenty-four women completed the study, but the PK analysis included data from 23 participants, as one was excluded for meeting outlier criteria. The results showed that LPCN 1154 met the bioequivalence criteria for Cmax, AUC0-∞, and AUC0-t compared to IV brexanolone. Moreover, LPCN 1154 had a higher Ctrough geometric mean than IV brexanolone, indicating sustained drug levels.

LPCN 1154 was well tolerated, with no reports of sedation or somnolence. Mild to moderate adverse events were observed, including venipuncture site reaction, headache, arthralgia, fatigue, dizziness, low back pain, and pelvic pain, none of which were severe or serious.

PPD is a major depressive disorder that can develop during pregnancy or within four weeks of delivery, with symptoms lasting up to 12 months. There is a significant unmet need for an oral, fast-acting product with better efficacy and safety to treat PPD. LPCN 1154, a bioidentical neuroactive steroid, aims to provide rapid relief with robust efficacy in a manageable 48-hour outpatient dosing regimen.

Approximately 500,000 women in the U.S. are affected by PPD annually, with an estimated 175,000 experiencing moderate to severe symptoms. Increased awareness among physicians and patients is expected to lead to higher diagnosis rates and more patients seeking treatment.

LPCN 1154 includes brexanolone, a bioidentical neuroactive steroid similar to allopregnanolone, which modulates the GABA receptor. It is specifically designed to offer rapid relief for patients with severe PPD and acutely elevated suicide risk, without posing significant risks to breastfed infants from brexanolone exposure.

Lipocine continues its efforts to develop differentiated, patient-friendly oral delivery options for large addressable markets with significant unmet medical needs. In addition to LPCN 1154 for PPD, the company is developing other clinical candidates, including LPCN 2101 for epilepsy, LPCN 2203 for essential tremor, LPCN 2401 for chronic weight management, and LPCN 1148 for liver cirrhosis symptoms. Lipocine is also exploring partnerships for its other candidates, including LPCN 1107 for preterm birth and LPCN 1154 for rapid relief of PPD.