MED3000 is a topical gel applied directly to the head (glans) of the penis for the treatment of male erectile dysfunction ("ED").
MED3000 works through a unique evaporative mode of action. MED3000’s combination of volatile components creates a novel action that stimulates nerve sensors in the highly innervated glans penis by a cooling and recovery warming effect, rapidly leading to smooth muscle relaxation, tumescence and erection as shown on the diagram below.
The glans penis is very highly innervated and there are sensors which are reactive to a range of physical sensations, including touch, pressure and temperature. Futura conducted further research and analysis in 2020 which demonstrated the mode of action for MED3000 as shown in the graph. MED3000 generates a rapid cooling and recovery warming action, promoting a sensory stimulation of the nerves on the glans penis leading to fast smooth muscle relaxation, tumescence and erection.
The 1,000 patient study included approximately 60 centres across nine Central and Eastern European countries. FM57 was a randomised, double-blind, placebo-controlled, home use, parallel group clinical trial. Patients being enrolled into FM57 for the initial four weeks had to attempt intercourse on at least four occasions in order to establish the severity of their ED, known as the pre-treatment ‘baseline’.
FM57, the Phase 3 study was designed to investigate the efficacy and safety of a range of topically applied gels using IIEF-EF and SEP 2 and 3 as co-primary clinical endpoints in mild, moderate and severe ED patients.
In study FM57, MED3000 was statistically significant in all three co-primary endpoints (IIEF-EF, SEP2 and SEP3; internationally accepted clinical trial endpoints in ED) against baseline (pre-treatment) data in addition to important, supporting secondary endpoints in terms of efficacy, speed of onset, duration of action and clinically meaningful differences in patient benefit.
FM57 demonstrated that MED3000 has the potential to be a highly effective, clinically proven, topical treatment for erectile dysfunction. MED3000 has a unique evaporative mode of action which the Company believes stimulates nerve endings in the glans penis by a cooling and recovery warming effect to cause an erection.
MED3000 results demonstrated a highly statistically significant improvement (p<0.001) in erectile function across ‘pooled’ patient severities (mild, moderate, and severe) as well as being statistically significantly superior within the separate mild, moderate and severe patient groups, compared to before treatment baseline, along with an excellent safety profile.
Data analysed was positive on measures of clinically meaningful benefit which physicians, patients and regulators view as increasingly important. MED3000 had a significant clinically meaningful effect in 60% of patients as calculated using the Rosen and Araujo statistical methods, standard assessment techniques for measuring Patient Reported Outcomes recognised and accepted by leading ED experts.
MED3000 begins to work immediately in some patients, with 60% of patients seeing onset of their erection within 10 minutes of application, substantially faster than reported for PDE5i's (oral tablets) with significant benefits for spontaneous rather than pre-planned sexual intercourse.
Overall, the level of efficacy was broadly equivalent to lower doses of current oral ED treatments. Safety and tolerability data were also highly positive, with no serious adverse events recorded in any patient, or their female partners.
2020 has been a year of tremendous progress from a regulatory perspective which resulted in Futura successfully making the case to EU and US regulatory agencies for MED3000 to be classified as a medical device available without the need for a doctor’s prescription (OTC). In April 2021 MED3000 was approved by the Notified Body as a medical device in the EU. Regulatory procedures, timelines and approaches differ by region.
In April 2021, Futura announced that it had received its MDR EU Quality Management Certificate for the placing on the market of MED3000 as a Class 2B medical device known as MED3000 ("CE mark approval"). Futura has previously announced in March 2021 that the EU Notified Body had successfully completed its review of the Company’s Technical Dossier for MED3000 with a recommendation to approve MED3000 for the medical device class and indication as applied for in July 2020. A Class 2B approval is by definition an approval allowing marketing of MED3000 as a non-prescription treatment across the European Union.
In order to obtain pre-marketing clearance within the EU under the new Medical Device Regulations, two requirements had to be met: submission of Technical Documentation which includes sufficient efficacy, safety and quality data; and demonstration that the Company can operate to a high standard of quality through a Quality Management System ("QMS").
With the CE mark granted, MED3000 becomes the first pan-European topical OTC treatment for ED. This paves the way for approval in many countries around the world, including in the Middle East, Africa, the Far East and Latin American regions which allow “fast-track” review based on recognition of the EU CE mark. The CE mark will also be recognised in Great Britain until 30 June 2023 and in the period leading up to this Futura will secure the new post-Brexit UKCA mark. This will be a streamlined process since it is understood the UK application can bridge to the EU approval.
FDA’s guidance documents indicate that their preference is to adopt an interactive and iterative approach to data requirements through pre-submission meetings with sponsors. According to FDA, careful considerations of their feedback may improve the quality of subsequent submissions, shorten total review times and facilitate the development process for new devices. Four productive and positive pre-submission meetings were held during 2020 and early 2021 to discuss existing FM57 Phase 3 clinical data, pathway to OTC status and any additional clinical and non-clinical requirements.
To date it has been established that an application may be made for MED3000 as a medical device for ED treatment, with a De Novo Classification. FDA requires an additional six-month small confirmatory clinical study, known as “FM71” taking a “least burdensome approach”, with detailed design now agreed. A short, small, non-clinical, Human Factors Study, testing accuracy of patient self diagnosis, ease of understanding of the OTC label and proving how to use the product correctly is also requested to support the regulatory submission and confirm the finalised OTC product label.
A fifth pre-submission meeting with FDA is planned for H2 2021 to agree the protocol for the Human Factors study which will commence and expect to complete by Q2 2022.
Futura has worked proactively with the FDA on the design of the requested supplemental clinical study to provide the FDA with the necessary reassurance of MED3000's efficacy for up to six months. FDA has endorsed the design of this study, FM71 based on the “least burdensome approach”. FM71 will be of a six-month duration (24 weeks) versus three-month duration for FM57 to reassure the FDA that efficacy does not diminish over a longer period of time, although it is Futura’s belief that this is unlikely as in the FM57 study efficacy improved from the first to third month of patient use.
Approximately 100 patients in total will be recruited including a mix of mild, moderate and severe ED sufferers. Recruited patient population will include 20 African American patients (from a leading US medical centre) and 80 patients recruited from Eastern Europe where sites include some of the same centres used in the FM57 trial. No placebo is required hence the study is relatively small in size. The primary endpoints are a significant change from baseline and exceeding a minimal clinically important difference calculated using the Rosen et al statistical method, a standard assessment technique for measuring Patient Reported Outcomes. Both endpoints were previously met for MED3000 over the 12-week duration of study FM57. Additional statistical study design has been agreed to support a fast speed of onset claim of 5, 10 or 15 minutes (10 minutes was achieved in FM57).
A Tadalafil 5mg (the active in Cialis®) comparator arm is included for informational purposes only to assess relative safety, speed of onset and overall efficacy. Non-inferiority of MED3000 against Tadalafil is not required to be shown. This will more accurately enable FDA to determine the relative benefit/risk ratio of MED3000 versus a commercially available comparator. Planning and preparatory activities for FM71 have commenced and the study is expected to complete in Q2 2022.
Run-in period to establish degree of patient's erectile dysfunction ("Baseline")
N = 50
Tadalafil 5 mg
N = 50