For several years now, a medical R&D company (Futura Medical) has been conducting clinical trials using a proprietary transdermal system with nitroglycerin (also called glyceryl trinitrate or GTN) for treating erectile dysfunction. According to company’s schedule, they are hoping to launch this product at the earliest in 2021, however it may be longer depending on how the approval process goes. They are calling the product MED2005 during the trial period and so far the results have been promising. With Phase 3 trials underway, there is a good chance this product will be available to men suffering from erectile dysfunction within a few years.
Clinical Trials for MED2005
The Phase 2 trial demonstrated the efficacy and safety of MED2005 in treating erectile dysfunction. In 44% of intercourse attempts, the onset of action occurred within 5 minutes. For 70%, the onset of action occurred within 10 minutes. No serious adverse effects were reported. If the results of this study are consistent with how the final product will work, this would make MED2005 the fastest-working treatment for erectile dysfunction.
In a pharmacokinetic trial, it was demonstrated that 75% of MED2005 was absorbed within 5 minutes. This is important as partner transference of the active ingredients may be an issue with a topically applied ED cream. While headache is a common symptom of using topical nitroglycerin cream, in trials of MED2005 to-date there has not been a significant increase in headaches when the dose is increased. With an increased dose there may be greater efficacy, especially for men with more severe erectile dysfunction.
The doses that are being studied in the Phase 3 trial are 0.2%, 0.4%, and 0.6%. Around 1,000 patients are participating in this study that is being conducted in Europe. Following this trial, another Phase 3 trial will be conducted in the United States based on the results of the European trial. If two of the doses show better results of the three, this trial will likely be used to compare the two in a cohort of 700 patients. Regulatory submissions are expected to start in 2020, and there may be an approved product in Europe sometime in 2021.
Why Use Topical Nitroglycerin?
PDE5 inhibitors have been the first-line treatment for erectile dysfunction since they were introduced in the 1990s. Drugs that fall into this category include sildenafil, tadalafil, and vardenafil (Viagra, Cialis, and Levitra, respectively). These medications are effective and have few side effects when used as directed. One major complaint however is that some of them need to be taken 30 minutes to an hour before sexual activity. In the case of tadalafil it may need to be taken daily to produce a cumulative effect. Planning when to take a medication can decrease the spontaneity of sex. A topical cream that works in less than 10 minutes could greatly improve spontaneity. If MED2005 is approved it is likely to become a new first-line treatment for erectile dysfunction.
Nitric oxide plays a key role in initiating and maintaining penile erection, so nitric oxide donors like nitroglycerin may be able to improve erectile dysfunction.
Nitroglycerin is actually used for a variety of other indications. The FDA approved medication Nitrostat includes 0.3mg, 0.4mg, and 0.6mg sublingual tablets. This is where the strengths in the MED2005 studies were derived from. Nitroglycerin relaxes vascular smooth muscle, which is what helps it increase blood flow to the penis to help maintain an erection. Because of its vasodilatory properties, it is prescribed to relieve chest pain caused by angina and to prevent chest pain during some physical activities. Nitroglycerin ointment is also used to treat anal fissures, by relaxing the muscles and improving blood flow so the fissure can heal.
All FDA approved versions of the PDE5 inhibitors that treat erectile dysfunction are taken orally. Nitroglycerin is being studied as a topical treatment. There are numerous possible benefits of using a medication topically. With a product like MED2005, gastrointestinal side effects can be avoided. The product does not interact with food or moderate intake of alcohol like PDE5 inhibitors. A topical cream that works fast can be used as-needed, without needing to plan an hour in advance to take a tablet. Most PDE5 inhibitors have a half-life that exceeds what is needed for sexual intercourse, while nitroglycerin’s is shorter and may result in fewer prolonged side effects.
Compounding Nitroglycerin Cream
Compounding pharmacies have been making products with nitroglycerin long before the MED2005 trials started. Treatments for anal fissures often contain nitroglycerin and these are frequently made in customized formulations. A nitroglycerin cream can be made by a compounding pharmacy specifically for treating erectile dysfunction. This cream will not have the same proprietary transdermal technology that is being used in clinical trials. However on its own it may still be effective for many men suffering from erectile dysfunction. If the MED2005 product becomes commercially available in the United States, it would be preferable to use that product. Woodland Hills Pharmacy makes a nitroglycerin cream in 0.4% or 0.6% strengths.
Important Warning about Nitroglycerin Cream
Nitroglycerin-containing products should never be used with any PDE5 inhibitors. The results of this combination can result in circulatory collapse and death. While separately the medications are relatively safe, together they can be extremely dangerous. Always consult with your doctor before starting a new medication.
MED2005 Clinical Programme – Futura Medical
Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study – The Journal of Sexual Medicine