Lipocine Inc. has achieved a significant milestone in postpartum depression treatment development by dosing the first patient in its pivotal Phase 3 clinical trial of LPCN 1154, an oral formulation of brexanolone. The Salt Lake City-based biopharmaceutical company announced this advancement on June 26, 2025, marking a crucial step toward providing women with a more accessible treatment option for postpartum depression (PPD).
Trial Design and Patient Population
The Phase 3 study is designed as a two-arm, randomized, blinded trial evaluating LPCN 1154 compared to placebo in women aged 15 years and older with severe PPD. Following FDA feedback, the study is being conducted in an outpatient setting with no requirement for medical monitoring by a healthcare provider, representing a significant advantage over the currently approved injectable brexanolone.
The treatment regimen involves a 48-hour dosing period, which was informed by dosing data from Lipocine's successful pharmacokinetic bio-bridge study with injectable brexanolone. The study is being conducted at multiple clinical sites across the United States and is registered under ClinicalTrials.gov ID NCT06979544.
Primary and Secondary Endpoints
The trial's primary endpoint focuses on the change from baseline in the Hamilton Depression Rating Scale (HAM-D), a widely recognized clinical measure of depression severity. Secondary endpoints include changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) to assess anxiety symptoms, along with key safety and tolerability measures.
The trial size is powered based on the treatment effect observed with the FDA-approved injectable brexanolone. Brexanolone is bioidentical to naturally occurring neuroactive steroid allopregnanolone, functioning as a positive allosteric modulator of γ-aminobutyric acid (GABA) receptor.
Addressing Unmet Medical Need
"Given the unmet need for rapid relief, this Phase 3 trial is an important step in our development program to bring LPCN 1154 to women suffering from postpartum depression," said Mahesh Patel, CEO of Lipocine. "By offering a novel bioidentical oral treatment with 48-hour treatment duration and expected robust efficacy, LPCN 1154 is designed to be a differentiated, rapid relief product with the potential to be the standard of care."
According to a recent survey by Truist Securities Research from January 2024, obstetricians believe approximately 20-40% of their patients may suffer from PPD. The condition is characterized as a major depressive disorder with onset either during pregnancy or within four weeks of delivery, with symptoms persisting up to 12 months after childbirth.
Current Treatment Landscape Limitations
PPD symptoms include hallmarks of major depression such as sadness, depressed mood, loss of interest, change in appetite, insomnia, sleeping too much, fatigue, difficulty thinking/concentrating, excessive crying, fear of harming the baby/oneself, and thoughts of death or suicide. Hormonal changes leading to GABA dysfunction are common in depression and pregnancy.
Traditional antidepressants, which are not approved for PPD, have slow onset of action, side effects such as weight gain, and do not demonstrate adequate remission post-acute treatment. This creates a significant treatment gap that LPCN 1154 aims to address.
Drug Candidate Profile
LPCN 1154 is expected to have characteristics that could be particularly appealing to patients with PPD, especially those with acutely elevated suicide risk where rapid improvement is a priority. The oral formulation presents no significant risk of adverse reactions to breastfed infants from exposure to brexanolone, addressing a key concern for new mothers.
Regulatory Timeline and Next Steps
The company anticipates using data from this Phase 3 trial to support a New Drug Application (NDA) submission of LPCN 1154 for PPD in mid-2026, with Phase 3 topline results expected in Q2 2026.
Lipocine will host a virtual research and development investor event on July 9, 2025, at 11:00 AM ET to discuss LPCN 1154. The event will feature Kristina M. Deligiannidis, MD from Zucker Hillside Hospital, Northwell Health, New York, who will join company management to discuss the current treatment landscape and unmet needs in PPD.
