Dr. Mel Spigelman
CEO and President
Dr. Bruce Carter
Chairman of the Board
Dear donors, stakeholders, partners, and patients,
This year has been another of significant change and achievement. Multiple waves of innovation are rippling through our once-stagnant TB drug development world. With our dedicated partners and new scientific approaches, we are accomplishing more than ever in a fraction of the time that would have been necessary a few years ago.
Positive results from the first regimen trial of PaMZ led to the initiation of NC- 002 — the first study that looks to realize the promise of treating drug-sensitive TB and MDR-TB patients with the same regimen. With the completion of patient treatment in REMox TB, we are closer to the first new product to shorten the treatment of drug-sensitive TB in almost 50 years. Meanwhile, we continue to identify even shorter potential regimens, ones that could treat TB in as little as six weeks and be used without concerns of pre-existing resistance.
We have built new partnerships in the discovery space and ramped up work to prepare for the launch of a moxifloxacincontaining four-month TB regimen. We are now collaborating more closely than ever with TB diagnostic scientists and developers to ensure new products will have their greatest impact and reach patients everywhere.
With the continued support of partners, donors, and stakeholders, we are poised to realize the promise of a revolution in TB care through the introduction of novel products. This revolution will be powered by innovation, leadership, and collaboration — all attributes to which we continually aspire.
Tuberculosis (TB) is a global pandemic killing nearly 1.5 million a year. The proliferation of drug-resistant TB has heightened the need for dramatically shorter and simpler drug regimens to treat and control the disease. Conquering this ancient killer is not possible without new treatments.
Today, the global pipeline of promising new TB drugs is larger than ever and transformative treatment is within reach. TB Alliance and partners are realizing this promise by developing the most beneficial TB regimens. Through innovation, we are working to bring faster, better, and affordable TB drugs to all.
In 2012, TB was responsible for
MORE THAN 5 TIMES as many deaths as all natural disasters combined
Goal is to select novel clinical development candidates to help stop the global pandemic
Establishes New Pathway to TB and MDR-TB Treatment. Goal is to find new treatment that takes months, not years, and cures multiple forms of tuberculosis.
Lancet paper finds novel drug regimen could be more effective than existing treatments; TB Alliance's trial to test drugs in combination saves years in research time
Tuberculosis must be treated with a combination of drugs. Therefore, in order to truly revolutionize TB therapy, regimens with multiple new agents are needed. TB Alliance and partners have established a game-changing R&D paradigm, allowing new TB drug combinations to be tested and brought to market more quickly than ever before. This new approach to regimen development powers our most recently launched and completed clinical trials of novel drug combinations.
To scientists, these flagship studies represent the cutting edge of TB drug development. To public health professionals, they represent an opportunity to develop the cheaper, simpler, and more effective tools needed to control and reverse the TB pandemic. To those affected by TB, they represent new promise for health and prosperity, everywhere.
In 2012, the results of the first novel TB drug combination trial NC-001 (New Combination 1) were published in The Lancet. These findings revealed that the experimental regimen PaMZ (PA-824 + moxifloxacin + pyrazinamide) killed more bacteria than today's TB treatment through the first two weeks of treatment.
This promising regimen may treat TB and many MDR-TB patients with the same totally oral treatment, thereby eliminating the need for injectable drugs. In doing so, it could reduce the length of some MDR-TB treatment by 80% and its cost by as much as 90%.
On World TB Day 2012, TB Alliance launched the NC-002 (New Combination 2) trial to test PaMZ for two months in TB and MDR-TB patients — the first trial to test a single regimen's ability to treat both drug-sensitive TB and MDR-TB. This trial is currently enrolling patients in multiple sites, helping to enhance clinical trial capacity for future regimen-development efforts. Positive results from this study would set the stage for pivotal Phase III registration trials of the PaMZ regimen.
TB Alliance uses a robust preclinical regimen-identification program to explore promising next-generation drug combinations. In 2012, TB Alliance also launched NC-003 (New Combination 3), the first clinical trial of second-generation novel regimens identified through this program. Four different second-generation regimens with the potential to further shorten treatment of TB, including MDR-TB, are being studied in this two-week trial.
The path to new TB drug regimens begins early on in drug discovery. To speed improved cures to patients, it is critical to stock the clinical development pipeline with promising new compounds, identify exciting drug combinations, and test them early in the development process. Preclinical testing of the PaMZ regimen allowed TB Alliance to rapidly advance the regimen into clinical trials.
This year, working with Johns Hopkins University on our preclinical combination-identification program, we discovered promising drug regimens. Using preclinical models, we have already identified regimens with the potential to reduce TB treatment to less than two months. Additionally, we have advanced a nextgeneration nitroimidazole, TBA-354. This compound, discovered in partnership with University of Auckland and University of Illinois at Chicago, is slated to enter clinical development in 2013.
Realizing the promise of better, faster-acting, and affordable TB drugs requires a global network of partners, each pushing forward that vision. TB Alliance collaborates at every level to help drive innovation through partnership — and in the process, provide improved TB regimens to those that need them.
Why is it important for GSK to work in TB drug R&D?
TB remains an area of significant ongoing unmet medical need. The challenges in finding the future combination regimens are huge and GSK is fully committed to playing its role in addressing these challenges.
What can be learned from working in TB drug R&D that can be applied to other strategic areas in your company?
At GSK, we are working in as open and transparent way as possible in our TB drug discovery efforts. We firmly believe the benefits of such precompetitive collaboration are clearly applicable to other tough areas of science that need to be understood before successful drug discovery can take place.
Why are collaborations between the pharmaceutical industry and PDPs, like the TB Alliance, a good fit for both parties?
It is a pleasure to work with the TB Alliance and frankly, an obvious compatibility. Our drug discovery experience coupled with the broad ranging knowledge of the TB field at the TB Alliance allows us to progress effectively and without unnecessary duplication.
How do you see the on-the-ground landscape of TB treatment changing over the next decade?
Over the next decade, I will be excited to see entirely new combination regimens for TB that deliver short, safe and effective benefit for both drug-susceptible and drug-resistant tuberculosis.
Briefly discuss some of the larger dynamics that will be critical to the success of TB R&D efforts
It is my personal view that we all — PDPs, pharma companies, academia — must cut through the boundary of perceived loss of value that inhibit entirely open collaboration in a field that is just too tough to be tackled alone. Then and only then do I believe we will see an escalation in progress towards our objectives. I sincerely hope that the work the TB Alliance and the BMGF TB Drug accelerator are doing in this regard, will lead the way.
Dr. Xiexiu Wang is the Honorable Director of TNT Centers for Diseases Control and Prevention and President for Chinese anti-tuberculosis association, as well as General Director of the Expert Committee for the TB Control working for the Ministry of Health.
What are the main problems you see with current TB treatment?
Right now, we use short course chemotherapy that is 6 to 8 months long. Soon after treatment, patients feel better and stop showing symptoms. They must take treatment for the full duration, but it's difficult for them because they feel better. This makes adherence a problem. That’s the main reason behind MDR-TB, and it becomes very hard to treat those cases. The long treatment leads to these other problems.
Why do you think it's important to support research for new treatments?
There are many advantages to shorter treatment. Adherence could be improved. The ability for patients to easily complete their treatment is most important. If we can shorten the regimen, this will get better. Also, we need new drugs for MDR-TB to treat cases more efficient[ly]. And, we cannot wait because there are lots of patients that need to have the new drugs and to use them as soon as possible.
You know, over the last 60 years nothing happened. In just the last 11 years there are now so many drugs under development. Some are already in clinical trials in China.
Why is it important for the TB Alliance to work in China?
My staff was very excited to initiate the REMox TB trial and they know it is very valuable for the Chinese, and also for others around the world. If Chinese doctors read the publications of trials in other countries, most will still want to do the trial again, in China. So, when we are part of a trial and show successful results, it's easier and faster for those results to be accepted by China.
How has the REMox TB trial helped to develop the professional skills of people working at the clinical trial sites?
Many of the REMox site staff members had not previously been involved in clinical research. Through continuous and extensive training, these site and laboratory staff members learned the basic principles of research, including adherence to the protocol with all the study documents, International Conference on Harmonization (ICH) Good Clinical Practice (GCP), and specific local standards and requirements.
As a result, we saw tremendous growth in the skills and capabilities of the sites and staffs. Where previously these sites operated as routine TB clinics or hospitals, they have now become research centersand acquired the skills to conduct clinical trials at ICH- GCP and local ethics and regulatory standards. These sites can now be utilized for other future clinical trials, also by other sponsors.
Do you expect these staff members to take on a growing role?
I'm reminded specifically of two laboratory staff members in Nairobi and Moshi who started out as laboratory technologists. During the trial, as they grew their knowledge on laboratory processes, they steadily took on more responsibility. After benefiting from training and mentoring, they were appointed as laboratory managers responsible for the conduct of REMox TB in their respective TB laboratories.
As a result of extensive training associated with the REMox TB trial, clinicians routinely treating TB patients became trialists and investigators, responsible for making crucial medical decisions and recording critical clinical data on REMox TB patients. Clinic nurses became research nursesor study coordinators for whom new career paths have opened.
Drivers at sites in Nairobi, Moshi, and South African sites are responsible for transporting samples to the laboratory within the required timelines and temperature conditions. They began these tasks knowing little to nothing of GCP and data recording techniques and processes, yet became the custodians of sample transport and may well play a vital role in future trials.
As a South African citizen, how do see the role of your and other endemic countries evolving in the future of TB research?
The TB Alliance is well-situated and staffed with experienced scientists to conduct and oversee clinical trials in Africa and around the world. With South Africa having an established clinical trial culture that goes back many decades, the TB Alliance is well positioned to share research expertise locally and with other nations by involving them in research projects.
As fellow Africans we understand the needs of these countries and can relate to their circumstances and culture. We are committed to continue training, coaching and mentoring other TB clinical trial sites in Africa.
With more trials being done in African countries we hope to see that communities and future patients will continue to be more eager to participate in clinical research. And, where there is still skepticism and resistance to participate in clinical trials, we trust that with a continuous flow of information, communities and patients will develop greater understanding of health issues to inform their decisions about medical care.
TB-endemic communities are essential partners in current and future research efforts and their roles are likely to expand in the future. This is an opportunity for us to spread our knowledge and for these countries to take a leadership role as well.
In 2012, the TB Alliance and its partners completed enrollment and treatment of patients in the REMox TB trial. This trial is testing a four-month moxifloxacin-containing regimen in drug-sensitive TB patients. If clinical trial results are positive, registration would be sought by 2014 in conjunction with our partner, Bayer HealthCare.
This new regimen would offer a shorter TB treatment for millions suffering around the world.
In preparation for results from the REMox TB trial, TB Alliance is augmenting the project's focus — from science and clinical trials to access — to ensure that an approved and beneficial product will be available as soon as possible to those in need. We have redoubled efforts to engage with high-TB burden countries, donors, the World Health Organization, and technical assistance agencies on issues from country and global decision making to uptake planning and product presentation.Close
A study conducted by the Liverpool School of Tropical Medicine, the National Institute of Medical Research in Tanzania, and BRAC in Bangladesh, in collaboration with TB Alliance, has documented the impact of TB treatment on patients. In the last two months of therapy, the economic toll of a patient's disease is equivalent to 90% of their usual earnings. Lost income and travel costs to reach the health center are both high.
A shorter regimen like those tested in the REMox TB trial would eliminate two months of these costs, thus greatly reducing a patient's burden - and helping to stop the cycle of TB and poverty.Close
For new regimens to have maximal impact, TB drugs and diagnostics must evolve in concert. Healthcare systems need tools to properly and accurately diagnose patients with TB. Simplified, low-cost drug-susceptibility testing would allow patients to be treated only with drugs to which they are sensitive — a modern standard too rarely used in TB treatment.
In 2012, TB Alliance signed a Memorandum of Understanding with the Foundation for Innovative New Diagnostics (FIND). This agreement paves the way for closer collaboration, priority setting, and information sharing. Through this partnership, we are developing a target product profile to inform diagnostics developers as to what tools are needed to complement new drug regimens in development. Such coordination will maximize the global impact of both new TB drugs and diagnostics.Close