Regulatory Beat: Biotech Firms Collaborate on Third-World Drug Development

After years of neglect, drugs and vaccines designed to treat a host of deadly diseases plaguing the poorer nations of the world, are in development, thanks to new political, social, and scientific advances. The Bill and Melinda Gates Foundation deserves special credit for placing vaccine development at the top of the research agenda for donor nations, nonprofit organizations, and manufacturers. The spread of the AIDS epidemic around the world and the looming pandemic flu crisis has brought home the threat of health problems in distant continents.

Jill Wechsler

In the past, manufacturers often donated treatments for third-world diseases, but did not invest significantly in new research. More recently, US and European governments offered tax breaks and patent extensions to "push" research for needed treatments that have little market value in industrial states; advance purchase commitments (APCs) aim to "pull" new products to market. But some analysts consider these tactics only minimally effective, often yielding therapies with low value for patients in poor countries; some products still are too expensive for widespread purchase and have dosing and distribution requirements that limit access and compliance.

NEW LANDSCAPE

Although governments and international agencies continue to back the push–pull drug development model, there is growing support for new partnership arrangements that seek to expand drug research by reducing the financial risk for manufacturers. This approach has altered the landscape for developing new drugs to treat neglected diseases, according to an important study by researchers at the London School of Economics headed by Dr. Mary Moran, now based in Australia. Published in September 2005 by the Wellcome Trust (London, UK), the report documents how public–private partnerships (PPPs) in the last five years have spurred R&D on new treatments for third-world health conditions such as malaria, tuberculosis, leprosy, leishmaniais, schistosomiasis, dengue fever and others report available from publishing@wellcome.ac.uk

While industry developed only a handful of new drugs to treat neglected diseases in the previous 25 years, Moran reports that from 2000 to 2004, partnerships involving large and small companies and nonprofit organizations launched 63 new research projects that should translate into nine or 10 new drugs by 2010. This investment has occurred largely outside normal government health funding programs, its support coming primarily from Gates, the Rockefeller Foundation, and other private donors.

In the 1990s, multinational pharma companies were closing down neglected disease research, according to Moran. Now pharma and biotech companies are investing their own resources in this area and joining PPPs, such as Medicines for Malaria Venture, the TB Alliance, Drugs for Neglected Diseases, and the Institute for One World Health (iOWH). Their participation may deflect criticism over industry's slow progress in addressing global life-threatening diseases, and also help manufacturers reach major emerging markets in India and China and tap their high-skilled researchers.

In addition, a growing number of niche biotech companies regard PPPs as prime opportunities to expand research programs. R&D partnerships provide vehicles for small companies to parlay expertise in genomics, bioinformatics, and other innovative technologies into new development activities, as well as gain opportunities to license intellectual property to larger partners. Relatively small markets for many infectious diseases are similarly attractive to biotech firms as are those for orphan drug development in the US and Europe. And both pharma and biotech companies anticipate that these low-profit R&D efforts eventually may yield spin-off products with commercial value in the West.

REDUCING RESEARCH RISKS

A main feature of PPPs is to reduce the cost and risk of neglected disease drug development for manufacturers. The new research model adopts a "no profit–no loss" approach that reverses traditional clinical development strategies. Partnerships encourage manufacturers to be more involved in relatively low-cost, early-stage research to identify and run preliminary tests on promising compounds. The more expensive and risky process of conducting clinical trials and seeking product registration in multiple countries is assumed largely by the nonprofit partner, which has local research networks and experience navigating national regulatory requirements. In addition to expanding the number of research projects for neglected diseases, PPPs aim to identify those efforts best able to deliver low-cost products of high value to patients in developing countries.

SCALING UP

Most collaborative projects rely on an industry partner to handle manufacturing and packaging of final drug products. Smaller biotech firms are likely to outsource manufacturing to a larger organization or developing-country partner. Those may include fairly sophisticated generics firms in India, China, and South Africa that have considerable expertise in formulation chemistry, low-cost scale up, and product distribution in Africa and Asia; some larger generic manufacturers are also gaining expertise in biotechnology formulation and production.

The search for effective disease treatments also may yield more-efficient and innovative formulations and manufacturing approaches. For example, iOWH is partnering with researchers at the University of California, Berkeley, and a spin-off company, Amyris Biotechnologies, to develop a large-scale, low-cost commercial microbial drug production process for artemisinin, the key ingredient in new antimalarials.

"Manufacturability" is an important consideration for identifying potentially successful products, says Jerald Sadoff, president of the AERAS Global Tuberculosis Vaccine Foundation (Rockville, MD, www.aeras.org), formerly with Merck. Most projects fail because they can't be made at an acceptable cost or in a reliable way for millions and millions of doses. Based on expectations that its R&D portfolio will yield effective vaccines in the coming decade, AERAS has built a $10 million research and manufacturing facility in Maryland. This investment permits AERAS to produce candidate vaccines that meet good manufacturing practices standards for use in clinical trials. Sadoff acknowledges that a new vaccine may not be available for widespread use until 2012, but believes that these early efforts set the stage for scaling up to produce the 150 million doses or more needed every year for a successful product.

PUSH FOR FUNDING

The limiting factor on all these initiatives is inadequate funding from wealthy nations. The Moran report notes that more than half the nearly $255 million contributed to PPPs as of April 2005 came from the Gates Foundation; the US provided $16 million, much more than other governments, but still very little. Most of public funding for third-world health currently goes to treatment programs such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria and the President's Emergency Plan for AIDS Relief (PEPFAR). These programs can "pull" new drugs to market, but have not stimulated new research on less visible diseases.

Jill Wechsler is BioPharm International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634, jwechsler@advanstar.com