A Bloodless Coup Against AIDS

A small Israeli start-up is hoping to tackle the AIDS epidemic in Africa with a medical device that allows circumcision to be performed pretty much anywhere and without recourse to a physician.

Does the solution to the AIDS epidemic in Africa lie in an office in Herzliya and a small plant in the Tefen Industrial Park in the Western Galilee? Possibly.

Over the past three years, the Israeli start-up Circ MedTech has developed PrePex - a simple medical device that allows male circumcision to be performed bloodlessly, without knife, anesthetic or a sterile environment, and without need for a physician. After completing the R&D stage and clinical and comparative tests, and after getting accreditation from the U.S. Food and Drug Administration, the company has started to sell the device in Africa commercially.

The device costs $20 apiece and could help governments reduce the number of AIDS victims in their countries by millions.

The company was launched in 2009, two years after the World Health Organization published a study recommending the circumcision of males in order to reduce their chances of infection with HIV/AIDS. The company's founders realized they could change the world, at a profit, if they could devise a way to perform circumcision safely, quickly and cheaply.

"Studies in South Africa, Rwanda and Kenya showed that circumcision reduces the chances of becoming infected by AIDS by 60 percent," says Tzameret Fuerst, company CEO and one of its four founders. "It's not 100 percent, but it's the closest there is."

Launched in 2007 with large-scale Western funding, the ambitious circumcision project seeks to prevent 3.5 million people from becoming new carriers by 2025. The method: circumcising 20 million men by 2015, which is 80 percent of the adult males in 14 AIDS-ridden African countries.

Five of the world's largest health and philanthropic organizations are involved in the project, including UNAIDS, the United Nations agency for AIDS prevention; PEPFAR, the U.S. President's Emergency Plan for AIDS Relief; the Bill & Melinda Gates Foundation; and the World Bank. The project is expected to cost about $1.5 billion and to save $16 billion by 2025, by reducing costs for treating the disease.

For the nonce, things have been moving slowly. Only about half a million men have undergone the process since the project was declared five years ago. Perhaps the start-up's technology can boost the pace.

In November 2011, PrePex got more tailwind when U.S. Secretary of State Hillary Clinton declared the goal of making the next generation an "AIDS-free generation." She listed three ways: blocking transmission of the virus from mother to child; widespread male circumcision; and extension of the treatment for people living with AIDS.

"In the fight against AIDS," she told a meeting at the National Institutes of Health in Bethesda, Maryland, "the ideal intervention is one that prevents people from being infected in the first place, and the two methods I've described - mother-to-child transmission, voluntary medical male circumcision - are the most cost-effective interventions we have, and we are scaling them up. But even once people do become HIV-positive, we can still make it far less likely that they will transmit the virus to others by treating them with the antiretroviral drugs."

Revolution in Africa

Eyes aglitter, Fuerst talks about the revolution that her small company - which has a total of eight employees in Herzliya - is about to foment in Africa. The 20 million African men slated to undergo circumcision in the near future are the company's market, she says: "I don't have to do a market analysis," she says. "The World Health Organization did it for me."

According to United Nations data, male circumcision reduces the risk of HIV infection by 60 to 70 percent in heterosexual intercourse, which is the most common method of infection in Africa. The reason circumcision is considered effective is that the foreskin contains cells that are particularly vulnerable to viruses.

Accordingly, since 2007 WHO and UNAIDS have been urging African countries with high infection rates to expand accessibility to safe circumcision services.

The procedure has not been found to slow down the disease's rate of spreading elsewhere, but in sub-Saharan Africa - a region that contains 12 percent of the world's population and 70 percent of the world's AIDS sufferers - researchers discovered that it has a significant influence. At the same time, though, other studies have not proved that circumcision reduces the risk of HIV infection, and the Africa Health Organization has come out against the project.

Last month Fuerst attended the International AIDS Society's biennial conference, held in Washington, D.C. She returned with invitations to supply devices for pilot programs in seven of the 14 countries that are included in the project. Together with Rwanda and Zimbabwe, where she is already operating, this gives her a foothold in nine countries already this year.

Genius of simplicity

This is the first media report in Israel about PrePex, though it has already been written about in The New York Times, Time magazine, the Financial Times and elsewhere. In Bill Gates' annual letter on behalf of the foundation he heads with his wife, he took note of PrePex and of its chief rival (a Chinese device ) as solutions for halting the spread of HIV transmission. "Even in the ancient practice of circumcision, innovation has the potential to make a big difference," Gates wrote. "The new PrePex and Shang Ring devices simplify the procedure and make surgery unnecessary." He also mentioned PrePex several times in recent weeks, including in a talk to students at Stanford.

Fuerst's partners in the company's establishment are the three entrepreneurs who developed the product: her husband, Dr. Oren Fuerst, who is the company's chairman; Ido Kilemnick; and Shaul Shohat. According to Tzameret Fuerst, the team has an accumulated experience of 70 years in the realm of medical instrumentation. Fuerst herself is from the business world and has no medical education. At this stage, she is in charge of sales in Africa and is effectively the company's only marketing person on that continent and in the world.

In addition to the employees in Herzliya, she has two African employees who assist in the clinical aspects and training people to use the device. The company plans to recruit more employees in Africa soon. The device is manufactured at Tefen Industrial Park.

To date, Circ MedTech has raised about $4 million for its PrePex activity. Acumen Fund, which describes itself as "a nonprofit global venture firm addressing poverty in South Asia and East Africa," invested $1.25 million. Acumen operates within a growing area of enterprise known as impact investing, in which investments are viewed not only through the prism of financial return but also in terms of their social and environmental impact.

Another investor is BTG Pactual, a Brazilian investment bank that is the largest institution of its kind in South America. The rest of the funding is from private investors, among them Ronen Bojmel, a New York-based Israeli who is a senior executive in Guggenheim Partners, a U.S. financial services firm; and Dr. Avraham Kadar, a pediatrician and entrepreneur who founded the children's educational website BrainPOP.

So far, the company has not sought scientific funding or other grants from the government. However, Fuerst notes, it is a reasonable assumption that Circ MedTech will have to raise additional capital in the future. The company has still not posted any profits.

Israeli start-ups usually work with the United States, Europe and the Far East. What's it like to work with Africa?

Fuerst: "It's challenging, because there are not many people who know how to do business in Africa, and I am learning on my own. I have been flying back-and-forth to Africa for the past two and a half years and have come to know the culture and the sensitivities, and am meeting brilliant people. I am shattering one myth after another. I have never encountered corruption there. The people I am meeting are smart and empathetic, and also care about their country. Still, although I am doing business in Africa, the money is Western, so I am not dependent on the payment ethics of Africa. I work with African governments but get paid by the U.S. government and other Western institutions."

The challenges facing Circ MedTech are somewhat different from those confronting most Israeli start-ups. In addition to technological innovation and smart marketing, there is also a need to overcome the shameful condition of the health system in AIDS-ridden African countries. Fuerst relates that in Rwanda, which is one of the major sites of the company's activity, only 300 physicians are coping with a population of more than 10 million. That represents 0.2 physicians per 10,000 inhabitants (compared with 36.5 in Israel ). "When you grasp the scale, you realize what Africa is confronting," Fuerst says. "Doctors face daily dilemmas of whether to assist women giving birth or circumcise men."

In the light of this state of affairs, Circ MedTech sought a solution in which nurses, too, would be able to perform circumcisions. Currently the company trains nurses within three days to carry out the procedure in the field. "We came up with the only solution that will bring about the circumcision of 20 million men by 2015," Fuerst declares. "The genius of the product lies in its simplicity. A few keywords guided the developers from day one: how to create a safe, simple device that can reach masses of people within a short time, and is cheaper than the surgical solution." The conditions in which the procedure is performed were also part of the constraints that Circ MedTech took into account. "From the beginning we imagined a nurse doing the procedure in a tent without electricity, hospitals or physicians. That was the development challenge we faced - and we succeeded."

The device consists of three elements. A special rubber band placed on the penis deprives the foreskin of blood and causes the skin to die, similar to what happens to a newborn's umbilical cord when it is clamped. Within a few hours the dead skin begins to shrivel, and within a week the device can be removed and the procedure completed. Putting the device in place takes only two minutes, and during the ensuing week life proceeds normally.

According to Fuerst, there is almost no pain involved, other than briefly when the device is removed. After its removal the wound heals, as in regular circumcision. "We are actually taking the sting out of a very frightening procedure," she says. "There are no injections, there is no blood, and you are back at work within five minutes."

The device was accredited by the FDA in America this January after a year-long wait, though the company did not need FDA accreditation in order to sell the product in Africa. "We did that as a declaration of the kind of company we are and how much safety and quality matter to us," Fuerst explains. "There are no compromises in these matters." The device also received European CE certification. Quality control is the reason PrePex is being manufactured in Tefen and not the Far East.

More than 5,000 men have undergone the procedure to date, 1,800 of them in clinical trials. According to a comparative study published in the professional journal JAIDS, the use of the Israeli device accelerates the process fivefold as compared with surgical circumcision. The study found no side effects for PrePex but seven in the surgical procedure, even though the PrePex sample was twice as large.

"Our method is not only faster than surgery, it is also safer," Fuerst says. "I hope that we will replace surgery in 90 percent of the cases. In 10 percent of the cases PrePex cannot be used due to anatomical reasons. I believe that because the product is safer, faster and cheaper, the entire market will move to us."

The PrePex device costs $20 in the respective countries. According to Fuerst, the cost of the procedure using the device is 30 percent less than the cost of surgery for the state. Still, the company is likely to set a higher price in the future for the private market. Fuerst explains that the marginal per-device manufacturing cost is not low, because the company adheres to the highest standards and because it is a medical instrument - though it looks like three simple pieces of plastic and rubber. Under the plan of the five global AIDS organizations to circumcise 20 million men at a cost of $1.5 billion, the average amount being allocated for the procedure is $75 per person.

No free brunch

Circ MedTech has made its most significant achievement to date in Rwanda, which adopted the company from its first year of operation. At present, Circ MedTech is running a model center there for those across the continent who are interested. More than 4,000 men have undergone PrePex circumcision in Rwanda, 900 of them in trials.

The PrePex first arrived in Rwanda two and a half years ago. Circ MedTech representatives met with the country's president, who was excited by the concept and invited Dr. Agnes Binagwaho - a pediatrician who was then director general and the permanent secretary of the Ministry of Health, and is now health minister - to get acquainted with the device. Rwanda has an impressive history in regard to adopting innovative health solutions. To cope with the minuscule number of physicians in the country, the government set up a system of 5,000 nurses and 45,000 community health workers. The minimum threshold for these workers is three years of schooling. These personnel are responsible for the initial medical response in villages, and it is through this infrastructure of nurses and community workers that Circ MedTech plans to reach the country's men and have them circumcised.

The Rwandan government last year announced a national plan to circumcise two million men - 50 percent of the country's adult male population - by June 2013. According to Fuerst, the government understood that attaining this target by surgical means would require 10 to 15 years, and decided to shorten the period. To obtain WHO authorization, PrePex needed to show positive results in clinical trials in two countries, but Rwanda preferred not to wait and decided to buy the device even before the official authorization was given. Health Minister Binagwaho launched a campaign to receive prior authorization to acquire the product.

Among other actions, she published an op-ed piece in the Washington Post last December titled "Male circumcision and the path to an AIDS-free generation." She noted that four million inhabitants of sub-Saharan Africa, "the hardest hit region in the world," can be saved by expanding "voluntary medical male circumcision - the best tool we have for HIV prevention." She went on to point out that the only method approved for funding was an expensive surgical procedure which could not be implemented owing to a dearth of surgeons and a lack of infrastructures. After elaborating on the clinical trial of PrePex in Rwanda, she noted, "We found that this device is in fact safer than the surgical method.

"Such simple solutions can be game-changers in the fight against HIV/AIDS. Public health officials set a goal to reach nearly 20 million men ages 15 to 49 by 2015, but in four years, Africa has reached less than 3 percent of its target goal," the health minister pointed out, adding, "It is time to reinvent the vocabulary for what is possible, and I propose to start talking about RMC, Rapid Male Circumcision, because the device we studied can revolutionize our prevention toolkit in Africa ... I call on the international community to effectively support the scale-up of Rapid Male Circumcision, through the more efficient nonsurgical devices that will make the procedure possible in countries with fewer skilled health-care professionals and surgical infrastructure."

Does the Rwandan government open the door to every start-up that develops a medical device? How did that happen?

Fuerst: "My husband and I met the Rwandan ambassador to the UN at a brunch. The brunch was hosted by one of our investors, and the ambassador, who had just taken up his post, was excited by the prototype we showed him. He asked for a promise that Rwanda would be the first country to try it. When we were ready, he fulfilled his side and invited us to Rwanda. We spent a week there and met with President Paul Kagame, the minister of health and the director general of the Ministry of Health, along with 20 health officials and army officers. The army is also having soldiers undergo circumcision.

"We went through months of evaluation by Rwanda's national ethics committee," she continues, "until they decided to let us carry out trials. They did a very rigorous check. There was a team of 20 physicians, out of the 300 in the country, and we had to answer a battery of questions. Our great fortune was that the president is a true visionary. I met with him and within 10 minutes he grasped the potential for his country and signed on. He immediately called in Binagwaho, who is also his children's personal physician, and I showed her the prototype. She said, 'I have circumcised people and I think it is safe.' That's how we started, because one person believed. We are here today because Rwanda had the foresight to adopt innovativeness."

Not a kosher alternative

The WHO was persuaded, and in March authorized the sale of PrePex in Rwanda. In the wake of that development, an additional 3,000 PrePex units were sold for use in the country. Rwanda is currently training nurses to use the device, with the aspiration of having 10,000 men undergo the procedure in the first stage. That will be a pilot for structuring the model by which two million men can be reached. The next country earmarked by Circ MedTech for sales of its product is Zimbabwe, where more than 1,000 men have undergone the PrePex procedure in clinical trials. Botswana has also given the go-ahead for a trial using PrePex.

To get authorization to sell the device in more countries, the WHO wants to see clinical studies proving that the device is safe for use; research comparing the procedure to surgery; and a study demonstrating that nurses can perform the procedure. To date, two of the three clinical trials being funded by the Bill & Melinda Gates Foundation have been completed in Rwanda and Zimbabwe. Once all the trials are done, the company will be accredited to sell throughout Africa.

Circ MedTech is in touch with corporations around the world in an effort to introduce the device into workplaces, so that employees can undergo on-the-job circumcision. In the future, the company plans to develop a solution for the circumcision of infants. That will help prevent the spread of AIDS in Africa among the next generation as well. In the meantime, infants and children have not been designated as a target by health organizations.

In any event, such a solution will not be suitable for those seeking a kosher alternative to Jewish ritual circumcision. "Our product is not according to halakha," Fuerst notes, referring to Jewish religious law. "Under halakha there has to be blood and the procedure must be immediate. This will upset many parents who have heard about the procedure and want us to develop a product for newborns."

Circ MedTech was given international recognition in May when it received the Technology for Health award from GBCHealth, which was founded by the late Richard C. Holbrooke, a diplomat who was U.S. ambassador to the UN. The organization (GBC stands for Global Business Coalition ) brings together 230 companies that work to improve the health of their employees and fights the spread of diseases and epidemics. The award citation noted that PrePex engaged in thinking outside the box to develop the solution and enlisted "supportive partnerships" such as the government of Rwanda and the WHO.

The simple solution and its vast potential give rise to the question of rival products. The only current competitor is a Chinese device called the Shang Ring, whose development began six years before that of the Israeli product but which has not yet received a WHO recommendation. According to Fuerst, PrePex is the only device that allows circumcision to be performed bloodlessly and without the injection of anesthetics, but the competitor also shortens the time of the surgery considerably.

You are a white woman who is in Africa to persuade men to undergo an intimate procedure. What kind of reception do you get?

"For the first 10 seconds people might feel uncomfortable, but I take a purely professional approach and they feel how much it means to me to foment change. I will not say it is easy, but I try to speak straightforwardly and professionally, and I think that neutralizes the embarrassment. There are also male gynecologists, you know. I treat the subject very naturally. I will not say I don't feel the embarrassment, but that doesn't stop me."

Aren't you apprehensive about the ability of the production line at Tefen to meet an order for 20 million devices by 2015? What does concern you?

"The pace of decision making by the governments. We are now on the cusp of the big breakthrough. It took time to overcome the hurdles of the WHO, and now the domino effect is coming into play. I am by nature an impatient person and it is very hard for me to wait for processes, because I know that every 16 seconds, someone in the world dies from AIDS - and when you know that fact, every second becomes vital. I don't have time." W