Meet the amazing cast behind a life-changing drug

April 19, 2017 by PATH

Eugenio de Hostos leads PATH’s work in drug research and preclinical development. Photo: PATH/Erika Amaya.

Eugenio de Hostos leads PATH’s work in drug research and preclinical development. Photo: PATH/Erika Amaya.

How one consortium is expanding drug options to fight parasitic worms worldwide.

It was well after midnight in San Francisco when Eugenio (“Geno”) de Hostos picked up the phone—but when his colleagues in China answered, he felt the familiar jolt of excitement.

He’d felt the same thrill at dawn, talking to his colleagues in Switzerland. At five, in a call to Maryland with the US Food and Drug Administration (FDA). And the previous week, chugging a cup of coffee while furiously scratching notes in a 6:00 a.m. conference call with project partners.

Geno leads PATH’s work in drug research and preclinical development, and for the last two years, he and his team—with pivotal support from colleagues at Swiss Tropical and Public Health Institute (Swiss TPH), the National Institute of Parasitic Diseases (NIPD) at the Chinese Center for Disease Control and Prevention, and Shandong Xinhua Pharmaceutical Company (XPC)—have been building a cast of global experts, partners, and funders to do something remarkable: get an underutilized, life-changing drug into the hands of communities affected by a debilitating neglected tropical disease.

The job requires many steps, including global registration. And now, bolstered by an innovative funding mechanism and a shared humanitarian goal, the partners are moving forward. Here’s what makes it possible—and what the next acts will be.

A hidden gem in China

Drug Development program leader David Shoultz (foreground, second from right) and several other people walking.

On a recent trip to China, Drug Development program leader David Shoultz (foreground, second from right) toured the facilities where tribendimidine (TrBD) is manufactured. Photo: PATH.

Worldwide, hookworm and other parasitic worms (what scientists call soil-transmitted helminths, or STHs) cause considerable harm. They’re a scourge on the world’s poorest communities—undermining nutrition, stunting growth, and increasing vulnerability to other diseases. And they affect a staggering 1.5 billion people.

To stop infection, affected communities often treat everyone with safe de-worming drugs. As part of mass drug administration (MDA) campaigns, this improves and save lives—but it may no longer be enough. The possibility of drug resistance and the sheer number of people worldwide in need of treatment amount to a pressing need for new and improved drug options.

An underutilized drug called tribendimidine (TrBD) offers hope. Discovered by Chinese scientists from NIPD and approved by the China Food and Drug Administration more than a decade ago, TrBD is a safe and effective treatment for STHs. But to help more people, it still must earn approval from the FDA and prequalification from the World Health Organization. Completion of both steps could unlock global access of TrBD for use in MDA campaigns.

The team got to work across public and private sectors to form the Tribendimidine Consortium and secure funds to move forward. Here’s the remarkable cast set on getting the job done:

The scientists

Safe, effective drugs start with science. We began with the experts at Swiss TPH. Recognized as a leader in global health, Swiss TPH has deep experience in research, services, teaching, and training. Long before PATH got involved, they were championing TrBD as an alternative treatment and tool to combat drug resistance. Their early guidance and long-standing relationships with key partners in China were crucial to move the work forward.

Swiss TPH led PATH to the scientists at NIPD in Shanghai, who know more about the drug than anyone—they developed it for China—and their insight and data were crucial after more than three generations of work by scientists at their facilities.

PATH’s scientists also rolled up their sleeves: laying the groundwork for a clinical development plan and organizing the body of evidence to navigate regulatory steps and get crucial applications and paperwork filed with the FDA.

The manufacturers

Six people in full lab suits stand in a hallway.

Colleagues from Shandong Xinhua Pharmaceutical Company (XPC) guided the PATH team through XPC to view work on chemistry, manufacturing, and controls. Photo: PATH.

There also needs to be someone to make TrBD safely, affordably, and to very high standards. A long-standing collaboration between Swiss TPH, NIPD, and XPC provided a reliable partner for that role. The original TrBD manufacturer, XPC is now working with PATH to ensure the drug is safe and ready for additional clinical trials.

The investors

Of course, developing drugs is also really expensive, but PATH was able to secure support from two leaders in impact investing. Our partners at the Global Health Investment Fund and the private-sector life-sciences investment firm Clarus saw the potential of TrBD and provided the early funding (and expertise) to get us off the ground—incentivized by social impact and an innovative FDA funding mechanism called a priority review voucher, or PRV.

Here’s how it works: A PRV is a reward for developing a drug or vaccine to treat a neglected disease. The reward entitles the bearer to a faster (but not less stringent) regulatory review for any other drug or vaccine under development. Time is money in drug development, so PRVs are extremely valuable and have been sold for more than US$300 million. Knowing this, the FDA uses the PRV program to incentivize development of tools for neglected diseases.

If PATH and our partners successfully bring TrBD through FDA approval, we’ll not only make strides toward improving health, but also earn and then monetize a PRV. And that promise—the chance to make an impact and do well by doing good—brought the investors on board.

A group of people stand around a sign that says "U.S. Department of Health and Human Services Food and Drug Administration."

The Tribendimidine Consortium’s work to secure FDA approval for TrBD will help to build the global framework for expanding treatment options for STHs and enabling access in endemic regions. Photo: PATH.

The role PATH plays

Of course, someone has to put all the pieces together, ushering the project from idea to scale. That’s PATH, and it’s what we’ve been doing for 40 years. Our scientific, drug development, and global health expertise mean that the manufacturers know we “get” what they do. The investors know that we understand their needs. And the scientists know we speak their language. And everyone knows our driving goal: to make better health possible by ensuring that every family has access to the appropriate health innovations they need to thrive.

All in for health

What’s next? Together, we’re planning clinical trials, preparing the drug, and building the package of materials for the FDA review. Approval can only be a few years away, and if successful, we also plan to sell our PRV, repaying our investors and dedicating a portion of the rest to making TrBD affordable and available worldwide. Proceeds from the sale of the PRV will also fund continuing research and development to keep driving down the global burden of STHs.

In the end, Geno—and the consortium—are all looking forward to one final call (at any hour): the moment we’ll announce a new tool to protect families everywhere from parasitic worms.