Last week, a British company called Futura Medical announced that their new erectile dysfunction (ED) treatment, MED3000, had been approved as a medical device in the EU. Futura's share price shot up shortly afterwards.
But MED3000 is no ordinary treatment. It is, in fact, possibly the first time in history that a company has knowingly commercialized a placebo.
Rise of a Placebo
MED3000 is a gel which is rubbed into the head of the penis to enhance erections. Futura state that it "is a highly effective, clinically proven, topical treatment for erectile dysfunction" with "60% of patients seeing onset of their erection within 5-10 minutes of application."
But what exactly is it?
MED3000 originated from Futura's efforts to treat ED with glyceryl trinitrate (nitroglycerin). Nitroglycerin is known to affect blood flow. The company created a nitroglycerin gel and called it MED2005, and carried out a randomized controlled trial comparing MED2005 to a placebo gel, which was identical except that it didn't contain any nitroglycerin.
The results of the first nitroglycerin trial were published in 2018. MED2005 performed slightly better than the placebo gel, but the difference was fairly small.
Futura ran a second trial of MED2005 vs. placebo gel. This study has not been published yet as far as I know, but Futura have revealed some of the results.
In the second trial, nitroglycerin MED2005 "did not achieve a difference" compared to placebo on the primary outcome measures. But both groups showed strong improvement in erectile function - even the patients on placebo. Boldly, Futura decided to turn the former placebo gel into a product in its own right, calling it MED3000.
Does it work?
MED3000 was recently granted a CE mark as an approved medical device in the EU. Does this mean it works? No. Unlike drugs, medical devices don't need to be proven efficacious to be sold; they only need to show conformity with safety regulations, which the CE mark indicates.
So how effective is MED3000 really?
The first thing to note is that MED3000 has never been shown to be more effective than any control treatment - because it was the control treatment.
When Futura describe the efficacy of MED3000, they are talking about improvement seen over the course of the treatment period (which was 1 month in the first trial, 3 months in the second), known as 'change vs. baseline'.
Large improvements vs. baseline are common in the placebo groups in clinical trials of a wide range of conditions. This improvement is sometimes attributed to the 'placebo effect', implying that the placebo caused the improvement. (Futura have used 'placebo effect' terminology - see below). But this is too simplistic.
There are many reasons why symptoms can improve over the course of a trial, of which the placebo effect is only one. To measure the actual effect of a placebo, we would need to compare the placebo to a control group who got no treatment at all. This hasn't been done for MED3000, but in trials of other placebos for various disorders, the effect of placebo over no treatment is often very small.
The vanishing FAQ
Even looking at the change vs. baseline, the improvement in the placebo (MED3000) group was actually very modest in the first trial. In response to the question "Has the treatment you have been taking improved your erectile function?", only 26% of patients answered "yes" for the placebo (MED3000).
In the second trial, MED3000 seemed to do a lot better. Why is this? Well, Futura themselves offered some interesting answers to this question on their FAQ.
Futura emphasized that the second study had a longer treatment period ("The study ran for 12 weeks versus 4 weeks where we noticed improvement in efficacy between 4 and 12 weeks.") They also pointed to "very strict compliance to the inclusion and exclusion criteria" and "greater emphasis on patient training and therefore compliance to the treatment regimen" in the second trial.
The problem is, if MED3000 makes it to market, the real world may not be like the second trial. In the real world, there are no exclusion criteria, because anyone could buy this product without a prescription. There will be no patient training, other than maybe a leaflet. In the real world, I doubt anyone would continue to use the product for over 1 month, if it's not working by then, to experience the benefits at 3 months.
Strangely, you won't find the above answers on the FAQ page currently. They seem to have been removed at some point in the past few days, but luckily I saved a copy from 19th March.
A placebo or not?
Something else has changed since the old version of Futura's FAQ. In the previous version, Futura seemed to accept that MED3000 was acting as a placebo. Describing the results of the second trial, they said that "the placebo effect was far greater than first indicated and presents an exciting opportunity in its own right."
But in the current FAQ, and across the current site, Futura seem reluctant to describe MED3000 as a placebo. They now say that MED3000 works through "a unique evaporative mode of action which the Company believes stimulates nerve endings in the glans penis to cause an erection."
There is no evidence for the evaporative mode of action from the clinical trials. To show that the evaporation is what makes MED3000 work, you'd need to compare it to a non-evaporative gel.
Overall, I don't think anyone knows how well MED3000 will work if it makes it to market. If it works, I don't think anyone could say how it works - whether it be the placebo effect, evaporation, or just, well, mechanical stimulation.
But I do know one truth - whoever it was at Futura who came up with the idea of marketing the placebo deserves an award for sheer chutzpah.