This document summarizes current treatments for premature ejaculation and discusses new treatment devices. It describes how botulinum toxin injections into the bulbospongiosus muscle have been shown to increase ejaculatory latency time in rats. A clinical trial also found botulinum toxin injections increased average intercourse duration in men. A new neuromuscular electrical stimulation device is being developed to contract the bulbospongiosus muscle during intercourse via electrical pulses, with the goal of immediately inhibiting ejaculation without drugs or surgery. Early feasibility studies found this device was able to delay ejaculation without adverse effects. Regulatory approval is planned in 2019. Transcutaneous posterior tibial nerve stimulation is also being studied as a potential non

1. Ege Can Serefoglu, MD, FECSM
Bahceci Health Group, Istanbul, Turkey
Medipol University, School of Medicine, Istanbul, Turkey

2. Disclosures
 Consultant: Virility Medical Ltd., Haifa, Israel

3. Medical Devices in PE Treatment
Introduction
Current Treatments
New Treatments

4. Introduction
 Ejaculation is the expulsion of semen from the meatus
 Constituted by 2 phases
 Emmision: Ejection of the semen into the posterior urethra
Contraction of testes, epididymes, VD, SV, prostate
 Expulsion: Ejection of sperm from urethra
Rhythmic contractions of perineal muscles (BS/IC)
Giuliano and Clement. Annu. Rev. Sex Res. 2015

5. Saitz and Serefoglu. Nat Rev Urol, 2015

6. Premature Ejaculation
 Affects 3 to 30% of the male population
 according to the definition used
 Cited as“the most common male sexual dysfunction”
 Causes important psychological problems
 Diminished self-esteem
 Anxiety
 Embarrassment
 Relationship problems
Serefoglu et al J Sex Med 2012

7. Treatment Advantages Disadvantages
Behavioural therapy
• High reported initial success rate in
uncontrolled studies
• Limited long-term efficacy
Topical anaesthetics (creams and
sprays)
• Effective in majority of patients
• Penile and vaginal hypoesthesia
• Female anorgasmia
• Skin reactions
Clomipramine • Significant improvement in IELT
• Nausea
• Erectile dysfunction
• HSDD
• Reduced vigilance
• Rhythm disorders
Antidepressant SSRIs*
• Significant improvement in IELT
• Generally require daily dosing
• Limited data on patient-reported
outcomes
• SSRI withdrawal syndrome
• Poorly accepted by patients and
partners
PDE5 inhibitors • First line option in PE with concomitant ED
• Arguable efficacy in only PE
patients
Tramadol
• Significant improvement in IELT
• Suitable for on-demand dosing
• Limited clinical data
• Limited real-life clinical experience
• Risk of addiction?
Saitz and Serefoglu. Nat Rev Urol. 2015
Current PE Treatments

8. Saitz and Serefoglu. Nat Rev Urol, 2015

9. Botulinum Toxin Injection

10.  Long-Evans rats (33 males)
 ~2 weeks to adapt to the light–dark cycle
 Treatment
 Placebo: Saline injection (0.1 ml)
 Low Dose: Botulinum toxin-A (0.5 U in 0.1 ml)
 High Dose: Botulinum toxin-A (1 U in 0.1 ml)
Serefoglu EC et al. J Sex Med. 2012

11. Bulbospongiosus Muscle

12. The Effects of Btx-A Injection on
Male Rat Ejaculatory Behavior
p=0.53
P=0.04*
P=0.013*
PLACEBO LOW-DOSE HIGH-DOSE
* Paired-sample T-test

14. A Safety and Efficacy Study of OnabotulinumtoxinA in PE
ClinicalTrials.gov Identifier: NCT01917006
0
20
40
60
80
100
120
140
160
180
200
Baseline Week 2 Week 4 Week 6 Week 8 Week 10 Week 12
Average IELT(seconds)
OnabotulinumtoxinA Dose 1 OnabotulinumtoxinA Dose 2 OnabotulinumtoxinA Dose 3 OnabotulinumtoxinA Dose 4
OnabotulinumtoxinA Dose 5 OnabotulinumtoxinA Dose 6 Placebo

15. Can we inhibit rhythmic BS muscle
contractions w/o drugs?
 intermittent electrical stimuli

16. Neuromuscular electrical stimulation
(NMES)
 Application of intermittent electrical stimuli to
superficial muscles
 triggers muscle contractions
 via the activation of the intramuscular nerve branches
 common and well-recognized tx to improve muscle
function
 PFM training with NMES has been used in many urological
problems (e.g. LUTS, SUI, ED)
Herzig D et al. the journal of injury, function, and rehabilitation 7 (2015)
McClurg D et al Neurourology and urodynamics 27 (2008)
Eder SE Women's health (London, England) 10 (2014)
Lavoisier P et al. Physical therapy 94 (2014)
Pastore AL et al. Ther Adv Urol 6 (2014)

17. At a Glance
17
Technology
Development
Patent I
Application
Completed Safety
Clinical Study
Patent II
Application
2015 2016 2017 20182014
Article I
Publication
Prototype
Finalized
Completed Feasibility
Clinical Study
Article II
Publication

18. NMES
Wearable,
discrete and
non-painful
Immediate
effect
Single-use &
disposable
Drug free
18

19. Competitive Advantages
Parameter NMES Desensitizers SSRIs
Effect onset Immediate 15 mins. 2 – 4 hrs.
Range of
effect
localized localized systemic
Duration of
effect
specific to
intercourse
exceeds intercourse
Adverse
events
minor
Numbness of
penis,
transference to
partner
nausea
ED
reduced libido
headaches
drowsiness
January 2019 19

20. NMESDevice

21. Clinical Feasibility Studies
21Shechter et al. WMSM Lisbon 2018.

22. Regulatory Status
February 19 22
US – Class II
• FDA approval planned
for Q4 2019
• Positive feedback from
FDA following pre-sub
meeting
• De-Novo pathway
EU – Class IIa
• CE approval planned
for Q4 2019
• Notified Body – BSI
• ISO13485:2016
compliance

23. Roadmap
February 19 23
2019 2020 20212018
Clinical
Initiated pivotal
study
Q1 2018
Product Dev
Device optimization completion
Q1 2019
Clinical
Pivotal study
completion
Q3 2019
Marketing
Initial sales
Q1 2020
Clinical
EU post marketing
study completion
Q1 2018
Regulatory
FDA and CE
mark approvals
Q4 2019
Clinical
Initiate post marketing
studies
Q1 2020
Clinical
US post marketing
study completion
Q1 2021
BizDev
Series A
Q1 2019

24. Other Devices
 Transcutaneous Posterior Tibial Nerve Stimulation
(TPTNS)
 Neuromodulation device (Morari®)

25. Transcutaneous Posterior Tibial
Nerve Stimulation (TPTNS)
 TPTNS is an effective therapy for controlling urinary
incontinence.
 Its efficacy in inhibiting the ejaculatory reflex is evaluated
 Phase II clinical trial, 26 pts
 3 TPTNS therapies per week for 12 weeks
 Frequency 20 HZ, pulse width of 200 microseconds, for 30 mins.
 The IELT and the PEDT scale was evaluated
Saffon et al. ESSM 2019

26. TPTNS
 52.9% of patients had at least tripled their baseline IELT
(p=0.019)
 mean IELT had increased 5.4 times (CI 95% 2.3 - 8.4)
 PEDT score decreased 5.7 points on average
 1 episode of constipation, 1 pt reported a sensation of heat in
the leg during one therapy session.
2.9
5.2
6.3
0
2
4
6
8
10
6 weeks End of therapy 3 months follow-up
Times the IELT increased
Saffon et al. ESSM 2019

29. Transdermal, non-invasive wearable device
using neuromodulation to delay ejaculation

30. Thank you…
egecanserefoglu@hotmail.com