The race to replace Viagra | Science

AAre we witnessing the end of an era for Viagra and Pfizer? Since the famous "little blue pill" exploded on the market in 1998, becoming the best selling drug in history, the US pharmaceutical giant has made huge sums by marketing it to people suffering from erectile dysfunction in the world. whole world. Three months after its launch, Viagra had already returned $ 400 million to Pfizer and, over the past two decades, it has consistently generated annual sales in the range of $ 1.8 billion.

However, this will soon come to an end, as in 2020, Pfizer's remaining patents on Viagra expire definitively. A multitude of generic versions have emerged over the past six years, often in strange forms such as mint strips or breath sprays, with Pfizer's take on medication rights slowly slackening. These should soon invade the market, manufacturers jostling for a slice of the cake.

This will make Viagra more accessible and less expensive, but for the millions of men suffering from erectile dysfunction around the world, it could also bring good news in the form of indispensable therapeutic innovations. Since Viagra was launched, few truly new therapies have been developed. Although Viagra and similar drugs like Cialis and Levitra – all of which increase blood flow in the penis by blocking an enzyme called PDE5 – are effective in approximately 70% of patients, they come with significant drawbacks.

First, side effects are common, ranging from headaches to stomach upset. In addition, since Viagra takes more than one hour to work, it is necessary to schedule bad and, in the case of older patients, medications can often be inappropriate because of potentially dangerous interactions with patients. drugs for hypertension or hypertension. . For patients with the most severe forms of erectile dysfunction, often resulting from nerve damage due to diabetes or prostate cancer surgery, Viagra usually does not work.

The need for better treatment is particularly urgent, as erectile dysfunction seems to be widespread, with the global prevalence rising to 300 million by the middle of the next decade. Scientists have long wondered if this is simply because men are becoming more open to report their problems, or to a byproduct of other health problems. One thing is clear: the market is growing.

"There is a huge need for new treatments that work in the widest possible patient population while having a longer effect for improving spontaneity and reducing the stress of having to take them in a planned way," says Dr. Samit Soni, urologist at Baylor College of Medicine in Houston, Texas. "Many patients would like to be able to take something without having to worry about it for 30 days."

But for the moment, there are few options. The only alternatives to Viagra are drugs that need to be injected directly into the penis shaft to improve blood flow, or complex surgery to install penis pumps or prosthetic implants. Neither are particularly pleasant.

So why is it? While a handful of pharmaceutical companies have tried and failed to introduce rival drugs into the clinic, the sheer scale of the profit-making machine Viagra has created a monopoly, with most companies fearing this challenge, perceiving it as too big a risk. But experts believe that this could be about to change.

"For many years after the development of Viagra, our understanding of erectile dysfunction and how to correct it has changed little," says Soni. "But with the expiration of the patent, there is definitely a renewed interest in alternative ways to treat erectile dysfunction, and their use to develop new ideas that can be patented and provide a lasting benefit to the patient." industry."

Viagra 2.0

In the early 2000s, scientists at Futura Medical, a pharmaceutical company in Surrey, heard about a heart disease drug that appeared to induce erections by accident.

"There have been anecdotal reports that people have deliberately sprayed this product on their penis," says Ken James, Research and Development Manager at Futura. "These observations had been reported in the scientific literature and the company thought that there might be a business opportunity."

The reported effects were due to a particular molecule called glyceryl trinitrate or GTN, which causes dilation of the blood vessels in the penis, thereby increasing blood flow. But Futura was so intrigued by the fact that even though Viagra, Cialis and other medications need to be taken orally, that is, they reach the target area through the bloodstream and therefore interact with each other. with other body systems. GTN could be quickly absorbed by the erectile. the tissues through the skin. This meant that it could potentially be applied directly as part of a gel or cream, with almost instant results and no annoying side effects badociated with Viagra.

"Viagra and Cialis are fairly effective medications, but 50% of people stop using them within a year," James says. "60 to 70% of people have some degree of dissatisfaction with them. This shows that there is an opportunity if we can come to the market with something that addresses many of these concerns. "

Over the past decade, Futura has developed a GTN-based gel called Eroxon, which appears to be able to induce erection in patients with mild to moderate erectile dysfunction in five to ten minutes. Already nicknamed by some the new Viagra, it seems to have the potential to become the first truly innovative treatment for erectile dysfunction in two decades, and Futura has even temporarily set its potential commercial value at $ 1 billion.

After investors showed renewed interest in supporting new treatments for erectile dysfunction, Futura completed a clinical trial of 232 patients last year and launched a final phase III trial in 1,000 patients. which should be completed by the end of 2019. If successful, Eroxon may be clinically available in the next few years, although urologists remain cautious.

"The biggest question of this phase III trial will be how they compare the clinical effectiveness of that of Viagra," Soni says. "In the past, we have found it difficult to achieve similar efficacy with topical administration, but our understanding of how drugs can be absorbed through the skin into the blood has improved dramatically."

S & # 39; s attacking the most serious cases

But even Futura scientists admit that Eroxon should not help the most serious cases of erectile dysfunction, affecting about 20 to 30% of patients, usually because of nerve damage in the lower abdomen.

In the past, there were few options for these people, but over the past five years, the renewed interest in erectile dysfunction has seen research programs devote more time and effort to erectile dysfunction. money to clinical trials of a technology known as shock wave therapy. Unlike Viagra or Eroxon, this attempts to solve the problems causing the dysfunction by pbading low-intensity sound waves into the erectile tissues.

Scientists are still not quite sure how or why it works, but they still think that this leads to a form of regeneration of erectile tissue, promoting the growth of new blood vessels and cleaning the plaque. existing vessels. "Improving the function of these vessels results in improved blood flow and erections in these patients," says Georgios Hatzichristodoulou, who studies shock wave therapy at the University of Würzburg in Germany.

However, given the wide range of causes of erectile dysfunction, shock wave therapy is currently effective only in a subset of these patients, particularly those whose lesions result from diabetes or hypertension.

Hatzichristodoulou pointed out that there remains a need for additional data, a series of tests on shock wave therapy being underway in Europe and the United States. But compared to Viagra or Eroxon, one of the big promises of treatment is that it would not be needed on a regular basis. Instead, patients could simply undergo maintenance treatment every six months or every year.

More tempting still, trying to restore the natural function of the penis, he points to a final treatment, a hope that can still be realized in the years to come.

Searching for a complete cure

Even when Viagra is effective, one of the problems for those who must take it indefinitely is that it loses less effectiveness over months or even years.

"It's pretty common. Most patients will see their erection worsen after being on viagra for a while, "says Hatzichristodoulou. "They take Viagra for five, six or ten years, and on some days they think there is little functional improvement."

The desperation has pushed many patients to unscrupulous private clinics around the world that promise ultimate treatment, offering treatments such as shock waves, stem cell infusions, and platelet-rich plasma injections on a standard basis. unregulated. But all these therapies are very experimental – for example, shock wave therapy is currently only approved by the US Food and Drug Administration to stimulate wound healing, with scientists still working on the determination of the best doses of efficacy and long-term safety.

"There is particularly convincing data on shock wave therapy, especially for some patients," says Soni. "But he is still in an early phase."

Scientists hope that shockwave therapy will be ready for prime time in the next five to ten years, but longer-term treatments, such as gene therapy, could heal completely. In the Kaiser Permanente Research Division in Northern California, a group of scientists has identified a genetic switch that is considered unique for badual function. They believe that this switch plays a crucial role in controlling the cerebral signals at the origin of the erection. New genome editing technologies such as Crispr-Cas9 may one day allow scientists to reactivate this switch in patients.

"This genetic location is part of a pathway involved in different body systems, from pigmentation to weight, to badual function," says project leader Eric Jorgenson. "But what's exciting about this is that it seems to be very specific to badual function, which would target that place and not disturb anything in the body. But there is a long way to go to get there. We need to understand the exact part of the brain where this switch is active, and then try to target it in the mouse. "

As the genome edition is still an experimental concept, Jorgenson said that regulators would take time to convince themselves that it could be secure. "The first uses of Crispr-like technology will likely be in patients for whom the medical need for experimental treatment is more direct," he says. "You would need a very safe treatment before people allow it for erectile dysfunction."

Although gene therapy is a little out of the box, new treatments for erectile dysfunction are still under consideration for the first time in decades. As the era of Viagra draws to a close and funding for research increases, the field is in its healthiest state for years.

"There has been no real innovation in the treatment of erectile dysfunction for many years," says Soni. "These new breakthroughs and treatments bring enthusiasm to a field of health that has been rocked for a long time."