Striking from two sides … or more

TB Alliance and AstraZeneca form research collaboration to fight tuberculosis

Jeffrey Bouley
BANGALORE, India—The 2010 BIO International Convention served as the backdrop May 3 for the Global Alliance for TB Drug Development (TB Alliance) and AstraZeneca (AZ) to announce that they have entered into a research collaboration agreement to accelerate the discovery, development and clinical use of drugs to fight tuberculosis (TB), including multiple drug-resistant strains of the disease (MDR-TB). Financial terms were not disclosed.

Under the agreement, the TB Alliance and AZ will both contribute promising TB drug discovery projects into a joint portfolio that will be co-developed by both parties. AstraZeneca's projects are coming from its TB research center in Bangalore, India. The initial set of projects contributed by the TB Alliance results from its ongoing collaboration with several world-leading researchers at the University of Pennsylvania, Rutgers University and New York Medical College.

The joint portfolio will be resourced by a core group of scientists based at the TB research center in AZ's Bangalore operations, with expertise and funding provided by both organizations.

"AZ has collaborated with us for a long time now, since probably 2003 when they set up operations in Bangalore and we started to interact with each other," recalls Zhenkun Ma, chief scientific officer for the TB Alliance. "We've had a lot of informal collaborations in which we've found ourselves aligning to each other's objectives, and this was a deal that evolved more out of a maturing of the existing relationship. MDR-TB is the kind of thing that requires a lot of collaboration and sharing of resources. We saw the synergies in working together officially, combining our portfolios, completing projects quicker and reaching locations in shorter timeframes."

In sharing resources, the two entities hope to create "a seamless path to clinical-stage development" that will improve the efficiency of both organizations' research programs. By focusing on novel compound classes, the drug candidates identified by the collaboration are likely to be effective against both drug-resistant and drug-sensitive tuberculosis, the organizations assert.

"TB, and multi-drug resistant TB even more so, can only be fought effectively if you have multiple drugs in the overall pipeline," notes Balganesh Tanjore, head of the Discovery Research operation at AstraZeneca India. "Although it may seem counterintuitive, in some senses, bringing only one compound into clinical treatment is perhaps less effective than bringing none. To me, it is almost like introducing nothing at all, because you need multiple compounds to put together a treatment regimen. So combining pipelines like this is critical."

MDR-TB is of particular concern to AZ and the TB Alliance. Annually, some 1.8 million people worldwide die from TB, and this is in part due to long, demanding treatment schedules that prove too much for many patients, with the resulting erratic or inconsistent treatment leading to drug resistance, treatment failure or death. This, in turn, can be traced in part to the fact that today's TB drugs are nearly 50 years old and must be taken for six to nine months for drug-sensitive disease and up to 24 months for drug-resistant disease. Worse yet, nowadays an estimated one in five patients with TB is resistant to at least one of today's standard first-line TB drugs, according to the World Health Organization.

Promising compounds identified in this collaboration will also be tested in combination with other therapies as part of the Critical Path to TB Drug Regimens (CPTR), a cross-sector initiative intended to speed TB drug regimens to patients who need them.
CPTR launched in March, created by the TB Alliance, the Critical Path Institute, and the Bill & Melinda Gates Foundation. AZ was one of ten pharmaceutical companies that have been affiliated with CPTR from its inception.

"Collaboration is absolutely vital to developing the tools needed to truly revolutionize the way TB is treated and overcome the global TB epidemic," says Dr. Mel Spigelman, president and CEO of the TB Alliance. "AstraZeneca has a well-established TB drug discovery program and is a crucial participant in the Critical Path to New TB Regimens. Together, our research promises to bring important advances to TB patients in need."

"AstraZeneca is building a leading franchise in the treatment of infectious diseases, both through our own in-house research as well as through collaborations. This collaboration is part of the global partnership that will be needed to conquer the TB epidemic," adds Les Hughes, AstraZeneca's vice president of infection discovery.

Although AZ's portion of the work is centered in India, the entire network of AZ researchers and resources can be tapped, Tanjore notes, particularly the AstraZeneca unit in Boston, which is focused on antibacterial drug discovery.

The TB Alliance's Ma is optimistic about this work with AZ and other work with academic institutions and pharma companies. In fact, working with various universities, institutes and companies, the TB Alliance has one program in Phase III clinical development, two in Phase II, six in lead optimization and 14 in lead identification. Of those 23 programs, five involve AZ, making it one of the most active partners the TB Alliance has, formally or informally, running almost neck-in-neck with GlaxoSmithKline.

"The field has changed a lot in the past decade or so," Ma notes. "Ten years ago, there were almost no pipelines and few pharmaceutical companies working on TB. If you look around today, not only are there pipelines, but close to 10 compounds in clinical development for TB."


Jeffrey Bouley

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