Final Phase II data confirms SPONTAN® is six times faster than oral vardenafil
LTR Pharma (ASX: LTP) has confirmed that the final Clinical Study Report for the SPONTAN® Phase II pharmacokinetic study supports the interim results with full statistical analysis, completing the pharmacokinetic dataset agreed with the FDA for the planned U.S. 505(b)(2) submission. The report, prepared by independent clinical research organisation Southern Star Research, confirms SPONTAN achieves peak blood concentration in a median of 10 minutes (5 mg dose) versus 60 minutes for the 20 mg oral vardenafil tablet, a difference that is statistically significant (p<0.0001).
The completion of this dataset directly enables submission-enabling activities scheduled for 2H CY2026, with the pivotal Phase III study targeted to commence in 1H CY2027.
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What the pharmacokinetic data actually shows
The headline finding is speed of absorption. SPONTAN 5 mg reached peak blood concentration (Tmax) in a median of 10 minutes, and the 2.5 mg dose in 11 minutes, compared to 60 minutes for the 20 mg oral vardenafil tablet. That sixfold difference in Tmax was achieved at a quarter of the oral dose.
The Phase II interim results published in April 2026 first established the 10-minute Tmax finding across 27 subjects, with the final Clinical Study Report now confirming those numbers hold under full statistical analysis.
Exposure tracked dose closely across the SPONTAN doses studied. Doubling the dose from 2.5 mg to 5 mg approximately doubled exposure, and dose-normalised AUC point estimates were broadly comparable across all three treatments. Half-life was consistent across both routes, confirming that the principal difference between SPONTAN and the oral tablet lies in the absorption phase rather than elimination.
Exposure to the major metabolite (M1) was substantially lower for SPONTAN than for the oral tablet, an expected outcome given that intranasal delivery bypasses first-pass metabolism.
| Parameter | SPONTAN® 5 mg | SPONTAN® 2.5 mg | Vardenafil 20 mg oral tablet |
|---|---|---|---|
| Tmax, median (range) | 10 minutes (10–15) | 11 minutes (5–60) | 60 minutes (30–186) |
| Cmax (mean ± SD, ng/mL) | 8.9 ± 6.8 | 5.8 ± 4.9 | 19.8 ± 8.8 |
| Half-life (t½, mean) | 4.4 hours | 3.8 hours | 4.4 hours |
| Dose-normalised AUC0-inf (ng·h/mL/mg) | 3.6 | 4.8 | 3.2 |
| Accumulation ratio (5 days once-daily dosing) | 1.0 ± 0.9 | n.a. | n.a. |
| Serious AEs / Grade 3+ TEAEs / discontinuations | 0 / 0 / 0 | 0 / 0 / 0 | 0 / 0 / 0 |
Final Clinical Study Report results (SDS089 (SPONTAN)-PK-02; n=27, including 14 participants aged ≥65 years). Tmax is presented as median (range). Cmax and accumulation ratio are presented as mean ± SD. n.a. = not applicable.
Five days of once-daily dosing produced no drug accumulation, and no clear pharmacokinetic differences were observed between men aged 65 and over (who made up 14 of the 27 participants) and younger adults. Both findings address requirements agreed with the FDA at the Pre-IND meeting.
Safety profile adds to the picture
The safety analysis did not identify any new or unexpected treatment-emergent adverse events. Key findings across all doses:
- No serious adverse events recorded
- No Grade 3 or higher events
- No treatment discontinuations or study withdrawals
- Treatment-related events were predominantly mild and self-resolving, including nasal congestion and headache
- Profile consistent with known vardenafil pharmacology and the intranasal route of administration
Professor Geoffrey Strange, Chief Medical Officer, LTR Pharma
“The final report confirms the interim analysis and is consistent with the rapid absorption we demonstrated in our Phase I study… A median time to peak concentration of 10 minutes at a quarter of the oral dose, with no accumulation on repeat dosing and comparable pharmacokinetics in men aged 65 and over, gives us a complete, well-characterised pharmacokinetic picture. These results strongly support SPONTAN’s positioning as a rapid-onset, on-demand therapy.”
Why faster absorption matters for the ED treatment market
Oral phosphodiesterase type 5 (PDE5) inhibitors, such as oral vardenafil, typically take 30 minutes to over two hours to reach peak blood concentration. Published research indicates that dropout rates from oral PDE5 inhibitor therapy exceed 50%, with lack of spontaneity a consistently cited reason (Carvalheira et al., Journal of Sexual Medicine, May 2012).
SPONTAN’s intranasal delivery bypasses first-pass metabolism in the liver, which explains the lower metabolite exposure. Additionally, the study confirmed comparable pharmacokinetics in men aged 65 and over. Oral PDE5 inhibitors often require dose adjustment in older patients, making this a clinically relevant distinction.
The 505(b)(2) regulatory pathway allows a new drug application to rely partly on existing safety and efficacy data for a previously approved drug, reducing the overall development burden. SPONTAN’s pharmacokinetic dataset was specifically designed to FDA Pre-IND specifications to support this pathway, with the study design, endpoints, and geriatric cohort all agreed at the 2025 Pre-IND meeting.
What comes next on the U.S. development roadmap
With the pharmacokinetic dataset now complete, the U.S. development programme moves into a series of submission-enabling workstreams scheduled for 2H CY2026:
- CMC package finalisation
- Human factors validation
- Leachables testing
- Non-clinical toxicology
The pivotal Phase III study is targeted to commence in 1H CY2027, with the 505(b)(2) submission to follow. The completed dataset also supports ongoing discussions with potential U.S. licensing and commercial partners, as well as continued engagement with the Therapeutic Goods Administration (TGA) and regulators in other key markets.
Lee Rodne, Executive Chairman, LTR Pharma
“We now hold a complete, independently reported dataset, designed to FDA specifications, confirming SPONTAN’s rapid-onset profile and favourable safety, with comparable pharmacokinetics in men aged 65 and over. This is the evidence package U.S. licensing partners and regulators need to see. Our focus now is progressing SPONTAN’s U.S. development programme, from preparations for the Phase III study through to our planned 505(b)(2) submission, while converting our partnering discussions into commercial outcomes for shareholders.”
LTR Pharma’s pipeline extends beyond SPONTAN. The company has successfully commercialised its rapid-acting treatment technology in Australia, with ROXUS® a second intranasal erectile dysfunction spray in its pipeline. The company is also advancing OROFLOW®, a novel intranasal spray under development for the treatment of Oesophageal Motility Disorders, a debilitating group of conditions affecting swallowing function. The breadth of the pipeline positions LTR Pharma as a platform company built around its proprietary intranasal drug-delivery technology, rather than a single-asset story.
For readers interested in how LTR Pharma’s intranasal platform extends beyond erectile dysfunction, our dedicated guide to OROFLOW and the oesophageal motility disorder programme covers the ethics approval, the clinical study design, and the US$8.1 billion market opportunity the treatment is targeting.
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