There’s a difference between rare and neglected diseases, Valerie Pasquetto tells me as we sit in a small workspace in San Diego, California. It’s the home of a non-profit startup called Drugs & Diagnostics for Tropical Diseases (DDTD) where Pasquetto work as VP of operations. Founder and President Marco Biamonte is to her left, alongside a tray of ripe mangos that are perfectly on-brand.
The thing about rare diseases, she explains, is that despite the small patient populations they can be highly lucrative. There are solid patient advocacy groups and incentives for companies to pursue targeted therapies. R&D costs can be more than recouped by charging hundreds of thousands of dollars per patient per year for the eventual drug.
Neglected diseases, on the other hand, might affect millions of people worldwide. They’re neglected because there’s no money to be made selling tests or drugs, because the people affected are among the three billion worldwide that live on less than $2.50 a day. Unless there’s an immediate outbreak risk in the developed world, the developed world looks the other way.
In 2011, Biamonte began a startup journey that ultimately led him to a potential diagnostic for a neglected tropical disease. Instead of turning away when the economic reality sunk in, DDTD embraced the field and restructured to become a fully non-profit diagnostics company. It was a fork in the road.
“There are pros and cons both ways,” Biamonte said. “But the bottom line was; in my heart, I wasn’t doing this to make money and so it was very difficult for me to go and tell investors there would be a profit in it.”
Loa loa
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
The World Health Organization (WHO) has a list of 16 neglected tropical diseases. DDTD’s lead program is a test for loiasis (aka African eye worm), which doesn’t even make that list — though it affects over 10 million people worldwide.
Loiasis is caused by an infection with a nematode worm called Loa loa, which is transmitted by deer flies. It is considered endemic in West and Central African nations such as Cameroon, Nigeria, and the Republic of Congo.
While loiasis isn’t particularly debilitating in itself, the populations it hits are also affected by river blindness (onchocerciasis) and elephantiasis (lymphatic filariasis). And it just so happens that the treatment for those infections, Merck’s Mectizan (ivermectin), can in rare cases be fatal if the patient is coinfected with Loa loa.
“The adult worm lays a crazy-high amount of embryos in the bloodstream. In some extreme cases, it can be 100,000 – they call them microfilariae – per milliliter of blood.” Biamonte explained. “What happens when you take ivermectin is all those embryos die at once. And you have this mass of necrotic embryos in your system, including in the brain that causes some inflammation and encephalopathy.”
Patients can go into a coma and in rare cases, even die.
The side effects with ivermectin only occur in a small subset of patients infected with a lot of microfilariae. It becomes a very real threat, however, when mass drug administration programs are deployed. Merck has donated 600 million doses of ivermectin for the treatment of river blindness and elephantiasis. Those need to be deployed, but it’s not economically or practically possible to test every individual for loiasis before they get the drug.
Loa Antibody Rapid Test
In mid-May, DDTD announced the launch of its Loa Antibody Rapid Test. Designed with the ivermectin conundrum in mind, it’s designed to both rule-in and rule-out patients in the field.
The test is small, cheap, and stable at high temperatures for months on end. It requires just a few drops of blood, fed directly into a device that is roughly the size of a human thumb but around half as thick. The results are delivered like a pregnancy test; if a strip appears after 20 minutes then Loa loa antibodies are present.
It’s currently a research use only (RUO) tool, Biamonte stressed, which means it can’t be used to inform individual treatment recommendations. Instead, it works as a mapping tool.
A team of epidemiologists would be armed with the test and deployed to a region where the infections are common. They would test sample populations of perhaps 100 people from different villages, Biamonte said, feeding the information into a computer model that can predict the likelihood of an adverse event if the local populations are treated with ivermectin. Areas that are co-endemic with Loa loa could thus be excluded from the ivermectin-based interventions.
Beyond loiasis, the technology could be applied to other diseases and rapidly deployed in response to an epidemic. All that is needed are the small plastic test kits and a different reagent to identify the antibodies of interest.
While DDTD hasn’t yet run clinical trials (largely due to funding restraints) the diagnostic has been independently validated by Thomas Nutman, head of clinical parasitology at the National Institute of Allergy and Infectious Diseases (NIAID).
Staying afloat
Amazingly, DDTD has delivered this test to the market with funding and donations of roughly $500,000.
It hasn’t been easy. Biamonte discovered the hard way that the startup world is built around for-profit companies. The same kinds of channels just don’t exist for companies that can’t offer a return on investment. Even Small Business Innovation Research (SBIR) grants are out of reach because they require a for-profit component.
“These are things that, being a non-profit, worked against us,” he said.
The money it has raised has come through a mixture of grants and help from the Centers for Disease Control and Prevention (CDC), the U.K.-based Wellcome Trust, and San Diego philanthropists.
It borrows equipment and instruments from its neighbor, nanoComposix, with whom it maintains a close relationship. Other companies have gifted the team tools. The actual tests are manufactured by a San Diego-based company with facilities in Tijuana, Mexico.
Shockingly, for those coming from the for-profit life sciences world, the startup has also cut costs by not filing patents for its technology and test. It just goes to show how neglected these diseases are. There’s no one else in the wings willing to champion this cause and there’s definitely no money to be made.
According to Biamonte, the biomarkers that inform these sorts of tests often sit on the shelf for years before anyone attempts to turn them into a functional product. With no money, there’s no urgency — just a giant cluster of unmet needs.
Looking ahead, there is much more DDTD can do — provided they can get the necessary funding and support.
In November 2016, it announced a partnership with Janssen Diagnostics, a Johnson & Johnson company, to explore new approaches to detecting river blindness. The team is also working on partnerships with humanitarian organizations and the World Health Organization to get the loa test deployed where it’s needed most.
Long term, Biamonte would like to get it approved for clinical use. The team has so far bypassed the expensive clinical trial process by focusing on research applications. But there’s much more this test, the technology, and the dedicated team could do with some funding to keep them moving forward.
Photo: drpnncpp, Getty Images
