May 31, 2013 was a holiday in the offices of Israeli startup Circ MedTech in Herzliya. That was the day the report came out that the World Health Organization had officially approved the use of the medical device it had developed: PrePex.

The device is simple and cheap to make. It is used to circumcise adult males – without an operation and without anesthesia – and the goal is to reduce the risk of being infected by the HIV virus, which over time can cause AIDS. The WHO approval paved the way to begin distributing the company’s product in Africa.

At the time, Circ MedTech attracted a great of interest around the world and flattering coverage from a number of media outlets, including the New York Times, which wrote about the Israeli company that wants to save Africa from AIDS. The company even received a warm reception from Bill Gates, who wrote about PrePex in his annual letter from his philanthropic foundation in 2012.

It looked like Circ MedTech was well on the way to being a sure thing, and make a real contribution to humanity and save millions of lives, and make some money doing it.

But then reality got in the way, and the big hopes and aspirations were shattered. After beginning with great success in Africa, a series of events finally led to the company’s closure recently – after 10 years of operations. TheMarker has investigated what happened, using documents and interviews with people from the company, and has discovered that the PrePex device, which was meant to help prevent AIDS, was linked to a number of cases of death from tetanus in Africa.

The company said that the device is completely safe – but had to close down after the WHO imposed a number of strict and unreasonable demands.

Circ MedTech was founded in 2009 by Dr. Oren Fuerst, Tzameret Fuerst, Ido Kilemnick and Shaul Shohat. The patented PrePex device the company developed was unique in that it carried out male circumcision without the need of an operation. It is composed of two plastic rings with a third elastic O-ring that is fitted onto the penis, and which stops the flow of blood to the foreskin – which causes the foreskin to dry out. After a week, the device is removed and the dead foreskin is cut off, in a process that is supposed to be almost painless.

UN undertaking

Open gallery view Health care workers speak to residents during a door to door AIDS awareness campaign in Soweto township near Johannesburg, November 29, 2005. Credit: REUTERS

The company was founded in the wake of a plan by the United Nations and the WHO in 2007 to promote male circumcision as a way to prevent HIV infection and AIDS in Africa. Scientific research had showed male circumcision reduced by 60% the chances of being infected by HIV from heterosexual intercourse.

Almost all circumcisions are conducted by surgically removing the foreskin, while PrePex was a cheap, simple and available alternative that was appropriate for rural populations that did not have access to medical services.

Development was completed in 2012 and the device, which was manufactured in the Tefen Industrial Zone in northern Galilee, received approval from the U.S. Food and Drug Administration. The company refuses to divulge how much money was invested in it, but says operating costs over the lifetime of the company reached $20 million, funded by outside capital and revenues.

PrePex was the first device which was an alternative to an operation that received official WHO approval. Senior health and AIDS prevention officials treated the device as a real lifesaver. In an interview with TheMarker in 2012, Tzameret Fuerst, the CEO at the time, said the device would help to circumcise 20 million men by 2015.

In 2013, Eddy Horowitz was appointed CEO. He had been recruited to lead the company from the development stage to the commercial. The company began distributing PrePex in African countries as part of circumcision programs with government and philanthropic funding.

Rwanda was one of the first countries that purchased the device, which later reached other countries such as Kenya, Uganda, Zambia and Zimbabwe. In 2015, a competing Chinese product was approved, named the Shang Ring, which is based on a similar principle and does not require surgery either – but Circ MedTech said it was not worried because its device was a much better product. But this is when things began to go wrong.

Toward the end of 2014, the first reports began to appear in Rwanda and Uganda about three patients who were circumcised using PrePex, and a short time later had tetanus. Two of them died of the disease. A company document stated that about 60,000 people had successfully undergone circumcision with its product before the three cases were reported.

Tetanus is a sometimes fatal illness that is caused by a bacterial infection. The bacteria usually enter the body through a break in the skin, such as a wound or cut. In Israel and other developed countries, the disease has been almost completely eradicated through the use of vaccines – but in Africa it is still common and dangerous. This is why Circ MedTech recommended vaccinating patients for tetanus before using PrePex, as a preventive measure, while the danger was being researched.

At the time, the company was on the verge of signing a major, long-term agreement with Global Fund – the nonprofit organization The Global Fund to Fight AIDS, Tuberculosis and Malaria. As part of the agreement, the device would be sold widely – for $12 per unit – which was much cheaper that the original price of about $20. But to the Israelis’ total surprise, because of the reports of tetanus, Global Fund suddenly backed away from the deal after a long period of negotiations.

Tetanus cases emerge

Open gallery view a woman walks past a World AIDS Day banner in Johannesburg, South Africa, December 1, 2017. Credit: Denis Farrell,AP

Despite the cancellation of the project, Circ MedTech continued to distribute the device in a number of African countries, and reported sales of hundreds of thousands of units through 2016. Published studies showed very high levels of satisfaction from those who used it, with the exception of very specific complaints – such as a bad smell from the area of the penis while the device was being used.

Then it turned out that a number of other cases of tetanus has occurred. According to documents Circ MedTech submitted to the WHO in 2016, a total of six cases of tetanus were reported by PrePex patients in Rwanda and Uganda from 2014 through 2016 (including the three already mentioned above). The symptoms began to appear 10 to 13 days after the beginning of the use of the device. Four of these patients, ages 18 to 34, died.

Tetanus infections are still common in Africa, and cases have been reported of the disease after circumcision operations too. But it seems that such a number of cases in that short a period of time, out of a relatively small number of procedures, caused a bit of panic at the WHO. The organization was worried about the accumulation of the bacteria during the relatively long period PrePex was used – one week – and from the sores that formed from the removal of the foreskin.

At the same time, research led by Prof. Cindy Liu of the Milken Institute of Public Health at George Washington University was published, and it showed cases of a greater amount of bacterial growth in the genital region after the use of PrePex. The scientists hypothesized that this is what caused the unpleasant odors and a higher risk of tetanus. Later, the scientists explained: “In summary, our article does not and cannot prove that the PrePex device causes an enhanced risk of tetanus, but it adds to the growing body of evidence that this may truly be the case.”

Circ MedTech rejected these claims, equipped with their own scientific evidence prepared by tetanus experts, including Prof. Itzhak Brook of Georgetown University in Washington, D.C. His report criticized Liu’s research methods and said the risk of using PrePex is low, similar to that of using existing methods of circumcision. “The new methods are expected to reduce the number of aerobic and anaerobic bacteria and, consequently, the risk of local infections,” he wrote. The issue was discussed at the time in the media and on social network sites in a number of African countries.

During 2016, the WHO issued a dramatic announcement for the Israeli company: The organization changed its previous recommendation and stated that the risk of contracting tetanus was indeed higher when using PrePex, compared to the regular circumcision operation. The recommendation was unambiguous: Anyone who wanted to use PrePex should first be completely vaccinated against tetanus.

This was basically a death sentence for the product. In many places in Africa the tetanus vaccine is not available on a regular basis, and certainly not in remote villages. It seems the WHO was aware of the meaning of their decision, but decided not to take the risk anyway. Even though cases of death after regular operations were also reported, the WHO’s limitations applied only to PrePex treatments – because the project was approved and under the auspices of the WHO, while the regular operations were the responsibility of the national governments. In addition, this limitation was not imposed on the use of the Chinese Shang Ring, since no cases of tetanus infection were linked to its use.

Circ MedTech tried to fight the decree, and Horowitz sent a letter in July 2016 to the WHO, saying the evidence involved was based on unreasonable assumptions and imprecise data – and the use of PrePex is nor any more dangerous that the risk of tetanus in circumcision under surgical methods. But the WHO stuck with its instructions and the African governments fell into line.

In response, Circ MedTech began developing a new product that was supposed to overcome any doubts about the tetanus risk. The new device would have led to the removal of the foreskin within a single day – instead of a week – while keeping the rest of the benefits of the original product. The company said the new device was a big success in clinical trials with 1,500 patients in Kenya, Rwanda and Zimbabwe, but the WHO refused to drop its vaccination requirements for the new product, until it was provided with further evidence that the new product was safe.

Sales halted

Open gallery view Children dance to music while attending a World AIDS Day commemoration at Nkosi's Haven in Johannesburg November 30, 2019 Credit: Denis Farrell,AP

Circ MedTech stopped production and marketing of the device completely last year – after selling what it said was 1.5 million units. Horowitz told the media in Kenya at the time: “Circ Medtech, the PrePex manufacturer, was unable to remove unreasonable WHO-imposed restrictions which have materially disadvantaged the product as compared to other circumcision methods for several years now,” Horowitz said. “Consequently and with considerable regret, the company board has decided to abandon the PrePex program, effective immediately.”

Last August, the company decided to liquidate itself. By that time it employed a few dozen people in Israel and Africa. In a letter Horowitz to shareholders after it was decided to close the firm, he said: “Despite numerous requests, CMT has yet to receive any satisfactory explanation as to the World Health Organization determination that the proposed D0 protocol has a differentiated risk profile associated with tetanus compared with surgical and other prequalified male circumcision devices. … Given the current circumstances, with considerable regret, the board of the company has decided to abandon the PrePex program effective immediately.”

The company’s founders and executives are convinced that PrePex was completely safe and expressed their frustration with the WHO. They still believe they were unfairly treated because of extraneous considerations. The firm’s main complaint is that behind the decision to require tetanus shots were more than just medical considerations, but conservatism, organizational politics and commercial considerations too.

Horowitz told TheMarker that the WHO traditionally works with giant drug and medical equipment manufacturers, and they often set excessive prices for their products. Because the WHO is funded by public and philanthropic money, the organization was very “sensitive” on this matter. Horowitz said the WHO is very cautious about the giant drug makers, and this spilled over in their attitude toward Circ MedTech – a small company with only one product – as if they wanted to make money at Africa’s expense.

The company says the WHO wanted to increase competition in the male circumcision market and bring in more manufacturers to lower prices. But PrePex was on its way to becoming the default choice and the programs had no intention of offering an alternative alongside PrePex and the regular operations. Horowitz said the WHO “wanted “to create a choice to prevent ‘these evil American Israeli PrePexers’ from screwing them over price.” He accused the organization of overreacting bin response to the criticism it suffered over its handling the Ebola outbreaks in 2014.

Fuerst says that based on WHO statistics on circumcision and AIDS, the company saved over 250,000 lives. Now when there is no longer PrePex, millions will die because of politics and bureaucracy.

The World Health Organization did not respond to a request from TheMarker before this report was published.