Info & Opinion
March 25, 2019
With news about big data, Aetna, Covance, GNS, Scrip, Quintiles, PPD, Icon, BioClinica, Merge, Medidata and GSK.
With news about FDA, CTMS, PMG Research, Inclinix, EMA, Hemofarm, Parexel and the Korea Drug Development Fund
David Underwood of Quanticate says some firms are giving short shrift to the basics of clinical trials
With news about Roche, Quintiles, Allscripts, Janssen, SGS, Oracle, TriReme, OpenClinica and FDA
When the Institute for OneWorld Health goes to India to conduct a clinical trial, it bypasses heavily populated Mumbai or bustling Bangalore, where most global trials occur. Instead, OneWorld goes deeply rural—so rural that sometimes there's no infrastructure at all.
But that's where its targeted diseases are. OneWorld Health is the U.S.'s only non-profit drug-development company. Its objective is to make drugs for diseases that for-profit drug developers don't bother with, ones that affect the poor and offer no return on investment. That's possible with the support of the Bill and Melinda Gates Foundation, which has so far donated more than $100 million.
Many of the processes the organization uses are the same, OneWorld just has to go about them differently to keep costs down. Way down. “We are trying to provide affordable drugs, and if we want that, we have to have affordable drug development,” says Richard Chin, OneWorld's CEO.
Chin knows from drug development. Before joining OneWorld six months ago, he was CEO of the biotech Oxigene (Nasdaq: OXGN). Before that, he ran global drug development for Elan. Prior to joining Elan, Chin held various clinical and scientific roles at Genentech, including head of clinical research for the biotherapeutics unit, at one point overseeing the clinical development of about half of the drugs at Genentech.
Banning Bells & Whistles
So when Chin says there are no bells and whistles on OneWorld's trials, he's not being hyperbolic. Take the organization's studies on paromomycin, an injection for visceral Leishmaniasis, the world's second most deadly parasitic disease after malaria. OneWorld recently conducted three Phase III trials on paromomycin deep in Bihar, a state in eastern India known for extreme poverty and low literacy; it's the epicenter of the disease in India, with an estimated 250,000 cases annually. Getting there alone was a challenge.
“Bihar is several plane rides and a couple of hours car ride from a major city,” says Chin. OneWorld went into progressively more rural areas to reach patients. Its employees often had no pre-existing investigator sites. Indeed, they first had to construct clinics, then recruit and train doctors for the trials. Often the sites had no road access; shipping supplies was a struggle. And then there was the internet-access issue.
“There was no broadband in Bihar; in order to collect the data in a timely fashion, we set up our own Wimax antenna and talked the utility company into dropping a trunk line where we were,” laughs Chin. “That was one way of getting around the issue.” (Wimax is short for worldwide interoperability for microwave access, a networking system that can blanket a 30-mile radius with broadband access.)
In a subsequent paromomycin trial, OneWorld contracted with Voxiva to develop cellphone-based electronic data entry. Investigators were able to use their cellphone keypads to enter case report form data. “You kind of have to work your way around a lot of the logistical challenges. Luckily, cellphones are ubiquitous there, even in the most rural areas,” says Chin.
OneWorld's Bihar trials were successful. The injection cured the fatal visceral Leishmaniasis, also known as kala-azar, in 95 percent of study subjects—on par with other treatments that are far more expensive. Paromomycin was approved for use in India in 2006, and added to the World Health Organization's Essential Medicines List. The Hyderabad, India-based drug maker Gland Pharma agreed to sell paromomycin at cost ($10-$15 per 21 day course). The results of OneWorld's first Bihar study were published in the New England Journal of Medicine in 2007.
The organization is getting ready to start Phase IV studies on paromomycin in Bangladesh and Nepal. The point is to obtain more safety data and expand access to the drug.
Ironically, in an industry that is outsourcing more aspects of every trial, OneWorld has found that bringing work back in house can save money. When OneWorld first went to India and was seeking academic sites, it contracted with an international contract research organization (CRO). When it began to push into smaller cities, OneWorld switched to an India-based CRO, which was cheaper and knew the terrain better. For data management, OneWorld contracted with a CRO back in the states.
“It was the opposite of the way everybody else was doing things; we were in India, outsourcing things back to the states,” says Chin, who grew up in Korea.
But those CROs were just used to help the trials launch in India. OneWorld soon let the CROs go, training its own staff in India to do clinical and data management functions, and moved all operations in-house. The organization now has 20 employees in India, with another 25 at its San Francisco headquarters. OneWorld tries not to have to contract with external vendors. But when it must, it tries to get a discount. Do most organizations oblige? Yes, says Chin, usually. Though not always. "Our goal is to be at least 33 to 50 percent leaner," Chin says. "CROs in India are inexpensive, but doing it in house is even less expensive."
Also instrumental in keeping costs low is not being in a hurry. “We have the same quality constraints, but not the same time constraints,” says Chin. On top of that, OneWorld doesn't have to compete with CROs and sponsors for popular sites, since the company works in such remote locales.
The regulatory community in India was pleased with OneWorld. “They were very welcoming,” says Chin. “I think we had an easier time with them than the for-profits. We are not outsourcing our clinical trials—we are developing a drug in India for India. They liked that, and the fact that we were investing in and developing the clinical trial infrastructure there.”
Roche Lending Library
Next up for OneWorld: diarrheal diseases like cholera, rotavirus and shigellosis, the second leading killer of children under the age of five in the developing world. The institute recently partnered with Roche, which allowed OneWorld to review 780,000 compounds in its proprietary compound library and select as many as 40 new drug leads for further study in the area of childhood diarrheal diseases. OneWorld had help from high-throughput screening firm BioFocus DPI. The plan is to develop one or two, and advance them into preclinical and clinical testing within two years.
OneWorld is working on similar partnerships with other pharmaceutical companies. “There's a real desire on the part of big pharma and big biotech to be involved in something like this,” says Chin. “We provide an opportunity for them to do it without much cost to themselves.”
Chin adds that OneWorld's relationship with big pharma is solid and warm—in a word, nonconfrontational. That may not be the case at other nonprofits. Says Chin: “Most of us here come from big pharma; we have never been anti-big pharma. We're interested in working with them.”
One potential partnership is a collaboration with the University of California-Berkeley and Amyris Biotechnologies to bioengineer yeast, the source of artemesinic acid. That's the key ingredient in aureomycin, the most effective antimalarial medication. Right now, the medicine's price fluctuates according to the waxing and waning of the supply of yeast from wormwood plants, often keeping it out of the hands of the health systems of developing countries. If the collaboration's manufacturing strategy works, that may no longer be the case.
“We want to reduce the price of drugs, but also stabilize the prices. Our goal is to bring the price of aureomycin from $2,000 a kilo to several hundred [dollars] a kilo, and keep it there," Chin says, adding that OneWorld is in the process of transferring the technology to Sanofi Aventis, which has agreed to do a scale up and sell the bioengineered version of the drug at no profit.
Beyond treatments for specific diseases, Chin says OneWorld wants to shift the way drug development is undertaken in poor countries. “We're trying to change the model,” says Chin. “Twenty years ago, there was hardly any work done on neglected diseases. Now there is, and charitable organizations fund the process, which, as it has evolved, is very costly. The next stop for us? Bring the cost of trials down so we can lower the true cost of the drug. The way we look at it is: why spend money on parts of the process that have gotten so expensive when that money could have been used for sanitation? I think we can do that, at least for neglected diseases.”
—by Suz Redfearn