SOURCE: Johnson & Johnson
By: Steven A. Silber, MD, Compound Developer Team Leader, Flubendazole
One of the things that make me proud to be a Johnson & Johnson employee is the commitment and dedication of every person here to do the best we can for patients… especially for the world’s most disadvantaged. I am grateful to be leading the team working to more effectively treat lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness), two of the most debilitating tropical diseases in the developing world.
To quote a new report from Uniting to Combat NTDs, an initiative with which J&J is affiliated, neglected tropical diseases (NTDs) are “a group of infectious diseases that disproportionally affect the world’s poorest and most vulnerable populations. It is estimated that more than one billion people are affected by NTDs, including roughly 800 million children. Although these diseases are the most common infections amongst the world’s poorest, they have traditionally received little or inconsistent attention on international health agendas. Targeted commitments and investments from a range of partners over the years have reduced the burden of many NTDs, but significant gaps still remain.”
In January of last year, Johnson & Johnson committed to collaborating with public and private partners to eliminate or control 10 NTDs by 2020, in what are the largest coordinated actions to date in support of the World Health Organization’s NTD goals. Under the London Declaration on NTDs, we agreed to develop a new form of flubendazole as a potentially curative therapy for elephantiasis and river blindness. Currently available drugs suppress but do not eradicate these parasites.
Flubendazole, originally discovered and developed more than 40 years ago by “Dr. Paul” Janssen, is an effective treatment against another NTD known as soil-born helminthes, which are intestinal parasites. However, the original formulation is not absorbed and thus does not reach the adult filarial worms (macrofilaria) which live in the tissues.
Our goal is to develop a new bioavailable formulation of flubendazole that will kill the adult worms, which maintain the cycle of infection by producing millions of larvae (microfilaria) into the bloodstream. These larvae are then transmitted to other people by mosquitos, in a manner similar to malaria, maintaining the cycle of infection.
J&J agreed to reformulate flubendazole and conduct comprehensive IND enabling pre-clinical toxicology and pharmacokinetic studies. Assuming the pre-clinical development program is successful, we will manufacture clinical supplies, help to design and co-fund clinical development, and manage the regulatory activities necessary to gain approval for this compound.
Our global team includes the Drugs for Neglected Diseases initiative (DNDi), which receives major funding by the Gates Foundation; Pfizer, which has explored development of another macrofilaricide; and world renowned experts on parasitic diseases including Charles Mackenzie from Michigan State University and Tim Geary from McGill University.
In less than a year following our initial commitment announced in the London Declaration, we have developed a more bioavailable formulation of flubendazole (although we still need to improve it), and have executed a substantial portion of the preclinical program. We are on track for submission of an Investigational New Drug application in early 2014.
One of the keys to our success in such a relatively short time has been the tenacity and devotion of everyone involved to see it through to success. When the program first started, many of our colleagues donated their time (outside of their “day job”) to work on this project before they were officially assigned to the CDT. Just one example: in the days immediately following Hurricane Sandy, we thought we had to cancel a long-planned meeting of our entire global team due to the complex logistics imposed by the storm. However, there was such overwhelming support and determination from those involved to maintain our timelines, we were able to get everyone to the US and forged on.
If proven safe and effective in clinical studies, flubendazole would be the first curative therapy for river blindness and elephantiasis – creating a truly transformational and positive impact on the health and lives of millions of people around the world.
At Johnson & Johnson, we believe that collaboration is the key to innovation in healthcare, and is critical in our quest to solve complex problems. We are leading by example.
To read more about the progress in combating NTDs, including our progress on flubendazole, please see From Promises to Progress: The First Annual Report on the London Declaration.
KEYWORDS: neglected tropical diseases, ntd, johnson & johnson, jnj, Gates Foundation, uniting to combat ntds, tropical diseases