Erectile dysfunction (ED)
Pudafensine, Initiator’s most advanced drug program has successfully demonstrated efficacy in a Clinicial Phase 2a Proof-of-Concept study and in a Phase 2b study to treat patients who suffer from organic erectile dysfunction (ED) that do not respond or cannot tolerate the currently marketed drugs in the PDE5i class (e.g. Viagra®, Cialis®, Levitra®).
Pudafensine strengthens the natural erection response by having a dual-action, both a central effect initiating erection and a peripheral effect potentiating erection through smooth muscle relaxation. Pudafensine is aimed for treatment of organic erectile dysfunction in patients who have erectile dysfunction (ED) due to abnormalities of the penile arteries and/or veins. Most common risk factors for organic ED are diabetes, overweight, lack of exercise, high cholesterol, high blood pressure, and cigarette smoking. Since Initiator Pharma was founded and pudafensine acquired, all preclinical development of the drug candidate to enable an application for clinical trials (CTA) has been carried out by the company’s auspices. Pudafensine is developed as a tablet that is taken orally on-demand. It is the company’s goal to be able to create a new “First-Line” treatment (recommended treatment) for the large group of men who have organic erectile dysfunction, who are sub-optimally treated with PDE5i products or for whom PDE5i treatment is contraindicated.
In Q4 2023 positive results from the Phase IIb clinical trial with pudafensine (IP2015) was announced. The Phase 2b trial is a randomized, double-blind, placebo-controlled, parallel-dosing group trial studying the efficacy and safety of high and low doses of pudafensine (IP2015) and placebo in otherwise healthy patients suffering from moderate to severe ED. The study comprises 130 patients divided into 3 parallel arms receiving a higher and a lower dose of pudafensine and placebo, respectively, with treatment duration of 4 weeks with frequent assessments of erectile dysfunction, safety and pharmacokinetics. The study has been conducted at the MAC clinical sites in the UK.
The study demonstrated statistically significant efficacy on the primary endpoint (related to improvements in intercourse settings) compared to placebo [p=0.034] and baseline [p=0.046]. Furthermore, the results were consistent throughout the study. Several other clinical endpoints related to improved intercourse activities (obtained from the International Index of Erectile Function Questionnaire, IIEF-15) demonstrated significant effects compared to the baseline. The frequency and type of adverse effects were mild to moderate and comparable to those observed in the placebo group. There was no reporting of critical safety observations.
Pudafensine have shown effects in a human model of pain ie. in a clinical Phase I study in healthy subjects dosed with the drug pudafensine and challenged with a pain-inducing ingredient (capsaicin).
The Phase I study was a randomized, double blind, placebo controlled study in 24 healthy male subjects, investigating the effects on pain measures (hyperalgesia, allodynia, and subjects pain rating) of single doses of pudafensine, pregabalin as an active control, and placebo. The pain was induced by intradermal capsaicin. Pudafensine demonstrated a statistically significant effect on allodynia (p=0.049) and showed a dose-dependent effect on the measured pain parameters. Pregabalin (p=0.083) and IP2015 (p=0.051) tended to reduce hyperalgesia, although the effects on hyperalgesia were not statistically significant compared to placebo-treated subjects.