Phase 3 Trial of LPCN 1154 for Postpartum Depression Shows Positive Progress

Lipocine announced completion of a scheduled independent review by the Data Safety Monitoring Board (DSMB) of the ongoing phase 3 trial of LPCN 1154 (oral brexanolone) for treatment of postpartum depression.¹ The board recommended the trial continue with no modifications, after 30 patients completed at least the 7 day follow up visit.

The current phase 3 trial is a randomized, double-blind study evaluating LPCN 1154 in women 15 to 45 years old diagnosed with severe postpartum depression. In accordance with feedback from the US Food and Drug Administration, the trial is being conducted solely through outpatient settings and does not require monitoring by a healthcare provider. Across the US, 19 sites are participating in the trial. Of the planned 80 participants, 47 have completed dosing and there have been no treatment discontinuations, dose reductions, or serious drug-related adverse events. In the trial there have been no reports of excessive sedation or loss of consciousness. The primary outcome being measured is change in baseline Hamilton Depression Rating Scale (HAM-D) score compared with placebo from baseline to 60 hours after administration.² Secondary outcomes include incidence, severity, and causality of adverse events, change in HAM-D score from baseline to hours 12 and 36 along with day 7 and day 30, remission based on HAM-D score, and other depression or anxiety rating scales.

Patients included in the trial had a depressive episode that began after the 3^rd trimester and later than the first 4 weeks after delivery, were less than 12 months postpartum at trial screening, and had HAM-D scores indicating severe depression. Patients with a history of bipolar disorder, schizophrenia or schizoaffective disorder, experiencing active psychosis, a history of suicidal behavior within 1 year, or a history of a seizure within 6 months were excluded from the study.

"We are encouraged by the safety profile observed in our clinical experience to date with our oral product candidate comprising GABAA positive allosteric modulating neuroactive steroid with low sedation," said Mahesh Patel, PhD, chief executive officer of Lipocine, in a press release. "Target attributes of LPCN 1154, including superior tolerability, rapid relief, and a 48-hour treatment duration, could be a game changer in the treatment of PPD, a debilitating and life-threatening condition. We look forward to LPCN 1154 Phase 3 study results, expected in the second quarter of 2026," he added.

LPCN 1154 is an oral form of brexanolone being developed for rapid relief of postpartum depression. The drug may be particularly useful for patients dealing with symptoms of postpartum depression like acutely elevated suicide risk. It also may be useful for quick symptom improvement while not posing a risk of adverse reaction to breastfed infants from exposure to brexanolone. With postpartum depression, hormonal changes can cause gamma-aminobutyric acid (GABA) dysfunction, which this medication works to address.

Information from a second DSMB meeting and a safety update are targeted for the beginning of 2026. The study will continue as planned. Data from this trial are expected to support a 505(b)(2) NDA submission for LPCN 1154.

References

1. Lipocine highlights promising interim safety profile in phase 3 trial of LPCN 1154 in postpartum depression. Press release. November 18, 2025. Accessed November 19, 2025. https://www.prnewswire.com/news-releases/lipocine-highlights-promising-interim-safety-profile-in-phase-3-trial-of-lpcn-1154-in-postpartum-depression-ppd-302617859.html

2. A study to assess the safety and efficacy of oral LPCN 1154A in women with severe PPD. ClinicalTrials.gov. September 12, 2025. Accessed November 20, 2025. https://clinicaltrials.gov/study/NCT06979544