Manufacturers Tackle Neglected Diseases

The importance of using biotechnology capabilities to discover and produce novel treatments for diseases affecting the developing world was highlighted at the annual meeting of the Biotechnology Industry Organization (BIO) in May. A growing number of public–private partnerships involving manufacturers and nonprofit organizations have made progress developing new vaccines and drugs for malaria, tuberculosis, AIDS, and other infectious diseases. BIO announced plans to sponsor an annual conference on "Partnering for Global Health," starting next year, to bring together biotech companies with financial organizations to develop new models for collaboration.

Jill Wechsler

The need for novel treatments for neglected diseases raises new challenges and opportunities. Hundreds of new drugs are in development to treat cancer, asthma, and other conditions prevalent in western nations, but very few for third-world diseases, commented James Geraghty, Genzyme's senior vice president. He noted that efforts to find new solutions to production and formulation issues can support corporate R&D programs and provide a valuable psychological boost for employees; third-world product development is "not charity," Geraghty said, but "a strategic responsibility" for the industry that is vital for maintaining political support and for regaining public trust and goodwill.

Tadataka (Tachi) Yamada, president of the Global Health Program at the Bill & Melinda Gates Foundation, described his organization's continued support for collaborative R&D programs, noting that the private sector must be more involved in bringing new solutions to this area. Gates also is providing more support to companies developing basic platform technologies, such as vaccine formulations without cold chain requirements, and is looking at "microfinancing" opportunities to support small local ventures.

VACCINES CRITICAL

Much of the discussion about global health at BIO and the International Conference on Global Health in Washington a few weeks later reflected progress in developing, testing, and producing new vaccines to prevent and reduce disease. The Malaria Vaccine Initiative managed by Seattle-based nonprofit organization PATH now has a candidate vaccine from GlaxoSmithKline nearing Phase 3 clinical trials. PATH's Meningitis Vaccine Project is even further along in developing a low-cost (40 cents a dose) vaccine to prevent frequent meningitis epidemics across Africa.

The Aeras Global TB Vaccine Foundation is working with the Dutch biotechnology company Crucell NV to use its advanced vector and large-scale cellular production systems to develop new products. Aeras has established its own vaccine production facility, "It's just as cheap to establish a facility that meets good manufacturing practices (GMPs) as one for clinical supplies," said president Jerald Sadoff.

The big disappointment is lack of a vaccine to prevent or treat AIDS. Models for AIDS treatment alone are unsustainable, Yamada noted; with 45 million people infected with the disease, all ultimately will need second-line treatment, a situation that already is creating tension about access to and patent protection for these more effective therapies. It will be a "great failure of modern medicine," said Yamada, if collaborative efforts do not succeed in this area.

Vaccine research also has benefited from the surge in funding to prepare for disease pandemics and bioterrorist attacks. As part of the national campaign to prepare for disease pandemics, Project BioShield is providing R&D support for new vaccines to prevent anthrax and smallpox, among other plagues. A sign of progress is the recent contract awarded Bavarian Nordic of Denmark to stockpile millions of doses of its new, safer smallpox vaccine. The Biomedical Advanced Research and Development Authority (BARDA), which was established by the Department of Health and Human Services (HHS) in April 2007, is implementing new policies that extend federal support for testing and developing medical countermeasures. Pandemic flu vaccine development should be facilitated by a final guidance from FDA on developing and testing seasonal and pandemic influenza vaccines.

EXPANDING PRODUCTION

Success in new vaccine development, however, presents new challenges regarding global distribution and access. While vaccination may be the most cost-effective approach for improving worldwide health, the emergence of more effective preventives for a broader number of diseases raises questions about who will pay, who will control distribution, and whether multiple vaccinations raise unknown safety issues. Most vaccine manufacturing takes place in Europe and the US where companies are most likely to provide products first in the case of disease outbreak. Indonesian health officials have raised the issue in demanding access to vaccines developed with the help of bird flu viral samples collected from their sick patients.

To address this issue, the World Health Organization is working with donor nations (WHO) and manufacturers to expand vaccine production capacity globally and possibly establish a third-world vaccine stockpile. WHO awarded grants in April 2007 to build influenza vaccine manufacturing capacity in Brazil, India, Mexico, Thailand, VietNam, and Indonesia.

These efforts would gain from the development of adaptable, disposable biomanufacturing technologies. Biotech manufacturing facilities normally take years to establish and validate and are not amendable to quick response and diverse production. Now equipment makers are designing new systems that can be deployed rapidly, are less costly to build, and require less water and power to operate. Such biotech production systems are being developed now with larger production capacity, noted Parish Galliher, president of Xcellerex, which has a line of portable bioreactors with disposable single-use components for producing clinical supplies and a variety of biotherapeutics and vaccines. Many vendors are developing similar systems that can be used for multiple purposes. Germany-based Sartorius is working with Thermo Fisher-Scientific to produce disposable process containers for biopharmaceutical applications.

Government research programs, such as the Defense Advanced Research Project Agency (DARPA), supports an accelerated manufacturing of pharmaceutical (AMP) program, which seeks to develop rapid, flexible vaccine manufacturing systems. The goal is to establish a protein manufacturing platform able to produce 3 million doses in 12 weeks, which also would help provide low-cost drugs for the developing world. Similarly, the National Institute of Allergy and Infectious Diseases (NIAID) has established a process development section in its malaria vaccine development branch that is working on new methods for fermentation, purification, and scale up.

OPPORTUNITIES AND RISKS

Such developments are attracting interest from the financial community. Investment company Kleiner Perkins Caulfield & Byers (KPCB) has established a Pandemic & Bio-Defense Fund with $200 million invested in companies developing rapid deployment biological manufacturing systems, as well as new disease surveillance systems, portable diagnostics and broad-spectrum therapeutics, and multivalent vaccines. Pharmaceutical companies are looking for acquisitions and investment opportunities. Glaxo has purchased some small vaccine firms, while Novartis picked up troubled Chiron following its flu vaccine debacle in 2004. More recently AstraZeneca paid a premium price for MedImmune, which is expanding the market for its FluMist inhaled vaccine.

While vaccine R&D may be in the limelight, the risks continue to rear up. MedImmune has run into trouble with FDA over manufacturing violations for FluMist. FDA has raised safety concerns about Dendreon's new cancer vaccine Provenge, and additional analysis will delay approval of this potential treatment for prostate cancer at least another year. Many test products may never make it to market, but those that do may offer significant improvements in public health.

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