November News from BIO Ventures for Global Health

Q: You have been active in global health research and development for more than 10 years and were one of the first to embrace the triple bottom line business model. Can you explain the concept of a triple bottom line and how it has inspired and enabled your work?

Sure. For us, the triple bottom line begins with financial return for pharmaceutical risk-based assessment -- you never know if your product is going to work, and you have to be sure you're making substantial returns for this type of research and development investment. The middle line is global health -- we want to make sure our products will be available to the whole world: every country, every population, and really every person, regardless of what their social or economic status may be. And finally, the bottom line is a commitment to the environment -- sustainable harvesting, fair trade work practices with our employees and businesses in rain forest areas of the world, and benefit sharing to recognize the intellectual contributions of the knowledge of the healers and the shamans in those rain forests.

It is important to us that our whole business model work in a private company, for-profit setting so that we're not counting on subsidies -- or charities or grants -- and that this whole model is working with the higher volume business model of emerging countries.

Q: What made you decide to get involved in diarrheal disease research and development for people living with HIV/AIDS? How does this fit into your business model for success?

When we began our discovery process almost 20 years ago, our focus and target was on infectious diseases that have a symptom that you can see and you can discuss in a collaborative manner with healers and shamans in the field. And diarrhea, obviously, fits that requirement easily. So we ultimately found the plant from which we get Crofelemer, and the obvious place to put it in clinical development was in acute diarrhea. At that time -- in 1996-97, antiretrovirals were starting to be used on a broad basis and what the FDA was seeing was that diarrheal disease in HIV/AIDS patients had changed, but the symptoms and impact to the patient was still there. And so because of our mechanism of action, the FDA asked us to put Crofelemer in clinical development for chronic diarrhea for people living with HIV/AIDS. We had a really good first outcome, and then we were off to the races with a phase II trial.

From that point, our global business model came into play. We knew there was a brass ring blockbuster opportunity for irritable bowel syndrome in the Western world, and we already had two successful HIV/AIDS studies under our belts. Then we looked at the global health need to be sure we had a project that was addressing those who are most at risk for mortality and morbidity from acute diarrhea, particularly children in the developing world.

Q: On November 4, you and your partners at Salix announced positive phase III data for Crofelemer in the treatment of chronic diarrhea in people living with HIV/AIDS. Congratulations! What does this mean going forward? What could this mean for patients in the developing world in the future?

There are two important things that the study showed. The first is that the drug works really, really well. We set a really high hurdle for Crofelemer to work -- for all intents and purposes, the drug had to wipe out diarrhea in patients coming in with a history of at least diarrhea in urgency every single day -- and we surpassed the hurdle. The second thing is the trial design, which allowed us to demonstrate such power in the endpoints and such power in the P value.

Additionally, we have data on diarrheal patients from many emerging and developing markets, and there is statistically significant indication of efficacy in every single case. We've had no safety issues with the drug, which is really important as we think about how it can be used going forward in emerging and developing settings. You don't always have a health care professional who is monitoring the access to the drugs and that's just the reality of it. And so particularly when you're dealing with children, you want to be sure you have a really safe product.

The results of the trial are important for the developing world for three reasons. To begin with, a first approval in the U.S. could start a cascade to make it easier to get approval in other countries that tend to recognize the value of the U.S. FDA approval -- even if they don't accept it. The second is that the study demonstrated safety and efficacy in a chronic population. In many situations in the developing world, it's going to be used acutely, so again you have a higher hurdle that you've provided in the West, and now it's being used for something that's having a dramatic effect in emerging and developing economies.

And then the third relates to HIV diarrhea itself. Nowadays, many HIV/AIDS patients around the world are given the opportunity to have access to antiretrovirals. It's such a major achievement, to get antiretrovirals to patients in some of these areas that are poverty-stricken, what a shame if the patients fail or are not able to adhere because they're having diarrhea as a side effect of the antiretroviral or their HIV status blooming in an environment where there's a lot of infectious disease. The results of this trial lead us to fully expect that an acute product for all populations will be available in short order to help all those in need.