LTR Pharma’s SPONTAN Hits 10-Minute Onset in Phase II, Beating Oral Pill by 50min

LTR Pharma reports Phase II interim data confirming SPONTAN’s 10-minute onset profile

LTR Pharma has reported interim Phase II pharmacokinetic data demonstrating that SPONTAN (5 mg) achieved a median time to peak concentration of 10 minutes, compared with 60 minutes for oral vardenafil (20 mg). The results, drawn from 27 subjects who completed the dosing phase of the SPONTAN Phase II clinical study, maintain consistency with Phase I findings and provide the specific pharmacokinetic dataset requested by the FDA during Pre-IND engagement in 2025.

The interim analysis revealed a clean safety profile across all dose groups. No serious adverse events, no Grade 3 or 4 treatment-emergent adverse events, and no treatment-related discontinuations were observed in the dataset. The time to maximum plasma concentration (Tmax) range for SPONTAN (5 mg) was 10-15 minutes, compared with 30-180 minutes for the oral tablet comparator.

Final results, including full statistical analysis, dose-proportionality evaluation, and the complete safety dataset, are expected Q3 CY2026. The interim data are positioned to inform the Company’s planned FDA 505(b)(2) regulatory pathway, a submission route that allows reliance on the FDA’s previous findings for vardenafil whilst demonstrating the benefits of the novel intranasal delivery method.

What is Tmax and why does it matter for erectile dysfunction treatment?

Tmax refers to the time required for a drug to reach its maximum concentration in the bloodstream following administration. For patients, a faster Tmax translates directly to a faster onset of therapeutic effect.

Oral PDE5 inhibitors, the standard treatment class for erectile dysfunction, require advance planning. Onset times for these therapies range from approximately 30 minutes to over 2 hours. Published literature indicates dropout rates exceeding 50% for oral PDE5 inhibitors, with lack of spontaneity consistently cited as a reason for discontinuation.

The 10-minute median Tmax reported for SPONTAN (5 mg) versus 60 minutes for oral vardenafil (20 mg) addresses a documented unmet need in erectile dysfunction treatment. High discontinuation rates with existing therapies suggest a rapid-onset alternative may improve patient adherence and capture market share amongst men who discontinue oral PDE5 therapy due to delayed onset.

Geriatric population shows comparable pharmacokinetics to adults

The Phase II study enrolled 14 subjects aged ≥65 years within the 27-subject trial cohort. Analysis of this geriatric subgroup revealed a median Tmax of 10 minutes for SPONTAN (5 mg), consistent with the broader trial population.

Maximum plasma concentration (Cmax) values in the geriatric cohort were 7.3 ± 5.5 ng/mL for the 5 mg dose, comparable to the trial population value of 8.9 ± 6.8 ng/mL. The Tmax range in subjects aged ≥65 years was 10-15 minutes, matching the range observed across the full trial dataset.

This geriatric pharmacokinetic profile addresses a specific requirement established during LTR Pharma’s 2025 Pre-IND meeting with the FDA. Consistent pharmacokinetics across age groups may support broader labelling without age-based dose adjustments, unlike some oral PDE5 therapies that require dose modifications in older patients subject to final analysis and regulatory review.

No drug accumulation observed over five-day repeat dosing

The Phase II study included a multiple-dose evaluation (Part 2) in which subjects received SPONTAN (5 mg) once daily for five consecutive days under fasted conditions. Analysis of repeat-dose pharmacokinetics revealed an accumulation ratio of 1.0 ± 0.9, indicating no buildup of drug in the system with daily use.

This finding was a specific study objective agreed with the FDA and supports the on-demand dosing model for SPONTAN. The absence of drug accumulation suggests the intranasal formulation does not result in sustained plasma levels with repeated administration.

Key pharmacokinetic metrics from the Phase II interim analysis

The interim analysis compared SPONTAN (2.5 mg and 5 mg intranasal doses) against oral vardenafil (20 mg) across key pharmacokinetic parameters. Lower Cmax values for SPONTAN relative to the oral tablet are consistent with the lower dose whilst maintaining rapid systemic exposure.

Data are interim and based on 27 subjects. Final statistical analysis remains ongoing. Cmax expressed as mean ± standard deviation.

FDA 505(b)(2) pathway and next steps

The 505(b)(2) regulatory pathway allows pharmaceutical sponsors to rely on the FDA’s previous findings regarding the safety and efficacy of an active pharmaceutical ingredient (in this case, vardenafil) whilst demonstrating the benefits of a novel delivery method. This pathway typically requires less clinical data than a full New Drug Application, potentially reducing development costs and timelines.

LTR Pharma’s Phase II study was specifically designed in accordance with FDA Pre-IND guidance provided during a 2025 meeting. The study addressed key requirements established by the FDA, including characterisation of single- and multiple-dose pharmacokinetics, evaluation of drug accumulation following repeat dosing, and assessment of pharmacokinetic differences between adult and geriatric populations.

Statistical analysis of the 27-subject dataset is ongoing. Full results, including final pharmacokinetic modelling, dose-proportionality analysis, and the complete safety dataset, are expected Q3 CY2026. The complete dataset will support regulatory engagement in Australia, the United States, and other key markets as LTR Pharma advances its 505(b)(2) submission strategy.

Executive Chairman commentary

Lee Rodne, Executive Chairman

“The interim Phase II data are consistent with our Phase I findings and reinforce SPONTAN’s differentiated rapid-onset profile, including in men aged 65 and over, a group that often requires dose adjustment with oral PDE5 therapies. Importantly, no serious adverse events, no severe treatment-emergent events, and no treatment-related discontinuations were observed. This Study was specifically designed in accordance with FDA Pre-IND guidance, and we are now focused on completing the statistical analysis and progressing our 505(b)(2) regulatory strategy in the United States.”

Study design and clinical methodology

The SPONTAN Phase II study employed a randomised, open-label design agreed with the FDA during the 2025 Pre-IND meeting. Key design elements include:

• Phase II randomised, open-label study
• 27 healthy adult male subjects (14 aged ≥65 years)
• Part 1: Single-dose, three-period crossover with 3-day washout between treatments
• Part 2: Multiple-dose evaluation (5 daily doses of SPONTAN 5 mg)
• Comparator: vardenafil 20 mg oral tablet
• Primary endpoints: single- and multiple-dose pharmacokinetics, dose proportionality
• Clinical site: Scientia Clinical Research, Sydney
• Clinical Research Organisation: Southern Star Research

The inclusion of a robust geriatric cohort representing 52% of the trial population (14 of 27 subjects) reflects the study’s specific focus on addressing FDA requirements for age-related pharmacokinetic characterisation. Subjects were confined to the clinical research unit for a minimum of 15 nights to enable comprehensive pharmacokinetic sampling and safety monitoring.

The interim Phase II data address key FDA Pre-IND requirements and support regulatory pathway advancement for SPONTAN as LTR Pharma progresses towards 505(b)(2) submission. As a commercial-stage company that has already commercialised SPONTAN in Australia, the release of full results in Q3 CY2026 represents the next material catalyst for investors tracking the Company’s US regulatory timeline.

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