15 March 2019

Just when you thought ED was getting dull


Just over 20 years ago, when the US Food and Drug Administration (FDA) approved the use of little known compound sildenafil citrate for use as a prescription drug for erectile dysfunction (ED), ED wasn’t even a recognised medical condition.

But this little blue pill would change that, and fast.

Within a few weeks of Viagra’s launch some 40,000 scripts would be written.

Within a year the drug had had established itself in US pop culture, in part assisted by a coincidental relaxation in the US laws surrounding direct-to-consumer advertising of prescription drugs, which allowed the airways to be swamped with ads for the drug. In that first year it even served as the plotline for an episode of hit TV series Sex and The City. It entered the US vernacular.

It was the fastest adoption of any drug in the history of the pharmaceutical industry at that time, surpassing one billion dollars in sales in its first year.

Its success , as well as the subsequent success of two major competitors, Cialis and Levitra, which entered the market five years later, changed the economics of the pharmaceutical industry. In addition, Viagra set the platform for the growth and success of the pharmaceutical giant Pfizer for the next decade and beyond.

But financial implications aside, where this phenomenon has had its greatest impact is on the culture around and conversations concerning sexual dysfunction in men. Within a few years, the use of the medications had become normalised among men aged 50 plus.

Over time, the purported good safety profile of the PDE5 inhibitors became evident and, in the UK, Viagra was made available over the counter further increasing its popularity. Usage even started migrating to much younger generations of men. The stigma attached to ED and the need for medications has been gradually fading.

In the US in the last few years, online businesses specifically targeting the sexuality and lifestyle of millennial men – one even using hipsters as their models – have popped up and been quite successful. 

As well as style tips and treatments for male image issues such as baldness, a key marketing push for all these sites has been ED. The majority of these sites employ doctors to write scripts and have done deals with pharmacy chains to dispense the medications directly.

The founder of one of these millennial male sites, Hims, Anthony Sperduti, said that their whole marketing strategy was focussed on getting these medications out of their traditional hiding place in the bathroom.

“We wanted to do the opposite of that: the kind of packaging you’d be proud of. You could have it on a T-shirt or a hoodie or a candle,” Sperduti said. And they did – they put it on T-shirts and candles, which they sold to their customer base.

From a medical perspective however, nothing really has changed in Australia since 2003 when Cialis, took the challenge up to Viagra by presenting a different profile of activation.

That’s a long time for not much to change in the way of medication management. So when Italian based company, Menarini, recently decided to launch a new PDE5 with a different activation profile in Australia, local ED specialists ears pricked up.

Avanafil (Spedra), was actually approved for use in Australia in late 2016, but Menarini wasn’t ready to supply and market the medication locally until early this year. It’s  been available in some European countries for nearly 10 years now, so its safety profile, like that of the other major PDE5 inhibitors is well documented, as is its profile of activation.

And it’s this profile of activation which has some local ED experts, and the company, excited that Australian men will have access to a medication option that represents a fresh approach to ED treatment.

If you’ve seen any ads for the launch of the drug, you’ll get the picture fairly quickly (this publication has already run some). The ad’s major tagline doesn’t really mince words: “sex sooner”. The feature’s  graphic is a light switch turned to the “on” position. The message is simple.

Avanafil, at least at certain doses, works faster than any of the existing medications.

The science of this claim is of course a little complex.

Not waiting the recommended time commonly results in failure to launch

With all orally administered drugs, the plasma concentration generally reaches a single, well-defined peak called Cmax at a specified time called Tmax.

Cmax and Tmax can be affected by a number of variables to do with a particular patient’s metabolism, including things like food and alcohol intake.

It’s not a precise measurement that can be replicated across different patients or even in the same patient at different times.

This is particularly important in ED, as it turns out that “time to sex” between administration of the drug and the deed remains a major concern among the affected men.

Local ED expert, Dr Michael Lowy, says that he tells his patients that they must wait at least one hour before expecting results with Viagra and at least two hours for Cialis. But most don’t, he says.

“They say, I took Viagra, or I took Cialis and it didn’t work.

“If you don’t wait the time you don’t get the best effect.  I always tell my patients they need to at least plan for this. You have to wait,” he told TMR.

If the literature is to be believed Spedra, at its 200mg dose, does have a shorter Tmax than both Viagra and Cialis, with the suggestion the peak concentration may be reached as soon as 15 minutes after taking the new drug. But the scientific literature suggests 30-45 minutes as a more realistic time frame.

But even at 30-45 minutes, Spedra is beating the higher doses of Viagra and Cialis, which respectively have a Tmax of one and two hours.

Naturally, the Tmax has a strong correlation with the time to action, but Tmax is highly variable depending on the patient and conditions around their metabolism of food and drink, so while Spedra may well work faster than its competitors there is still likely to be a delay.

Dr Lowy says that although this is made clear to all his patients, the problem of not waiting is not likely to go away.

Studies suggest that 50% of men do not know they are going to have a sexual encounter before the encounter. A study quoted in the Spedra marketing then goes on to suggest that 50% of men fail to succeed in such an encounter because of the time to onset of effect of existing medications.

Says Dr Lowy, “ We find there are so many variables in how these drugs work for each person because there are so many variables in play.

“One will work better than another at a particular dose and there isn’t an easy explanation always as to why”.

More speed of onset then, might actually find itself a market. Particularly when you consider how the demographic and culture of ED treatment has shifted so substantively over the years. What is it they say about millennials being a little impatient?

Avanafil also works better if a patient has been drinking alcohol or eating, according to the literature.

Dr Lowy whose specialised clinic treats lots of patients recovering from medical procedures which have affected their sexual function says that both Viagra and Cialis are excellent medications.

But he thinks the addition of Avanafil to his arsenal of treatments, after such a long hiatus in treatment options, is a good thing.

“I think it’s about time we had something new and fresh,” he told TMR.

“It appears to be as efficacious as any other PDE5 inhibitor, but it seems to work a bit faster and I think that’s a big deal because many won’t wait the required time for the Tmax with Viagra and Cialis,” he said.

“The moment goes by, and often they [patients] don’t think the drug is working.”

As if you really needed to study the idea that speed is important, there are now studies reported in the peer reviewed literature, which reinforce in a scientific manner, the desire of men to have a drug that works faster.

As far as existing Cialis users are concerned, and for many new users, Dr Lowy doesn’t believe there is likely to be much change. He says that Cialis’ clinical positioning as a daily dose drug is important. “It’s an excellent drug, daily dosing is good habit, and it’s safe to use daily, even if you aren’t having regular sex,” he said.

This feature of Cialis, the cessation of heavy marketing by Pfizer, and likely the continued marketing of Cialis by Eli Lilly, have brought the use of each drug up in Australia to near equivalent market shares. But Cialis recently won a local court battle to continue its patent in this country and Viagra is off-patent so pricing is vastly different.

Daily dosing, as good as such a habit might be, can be an expensive habit given Cialis’ on-patent status, and that can be an issue for some patients. Some reports have patients trying to trick the medication management protocols by cutting their Viagra or equivalent generic into quarters and dosing themselves daily. There is no evidence that such a strategy would work, according to Dr Lowy. But he says it does point to issues around pricing of the medications for some classes of patient.

If you go to any of the local online websites you get a fairly good indication of the different pricing between each of the medications.

On Pharmacy Direct Cialis 5mg (the daily dose) will set a patient back $192 for a pack of 28, or $6.86 per pill.

Viagra at its 100mg dose is just $3.50 per pill. Which might explain the odd behaviour of some patients trying to trick the system and get a daily effect.

Spedra will come onto the market at a recommended retail price of about $12.50 per pill at any strength.

So rather than price, the Spedra marketers are probably thinking that speed is their unique proposition. 

If you believe the data on failure to launch due to Tmax times, then there may well be market for a drug that men might carry with them, much like they might carry a condom, in readiness for a sexual encounter.

Dr Lowy thinks there probably is a place for Spedra in Australia as something new for GPs to offer patients in certain situations, especially where other medications aren’t working.

Apart from anything else, he quips, “It’s something fresh to talk about” in your ED discussions.

Disclosure: The Medical Republic has accepted display advertising from the supplier of Spedra, Menarini Australia.

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