New R&D models needed to tackle drug-resistant TB

Access to treatment varies from country to country, depending on the strength of health care systems and ability to buy drugs that can cost thousands of dollars. TB is treatable and curable, but 1.5 million people died from the disease in 2013.

Delegates from all around the world came together last month in Barcelona, Spain for the first international parliamentarian TB summit, where attendees declared a commitment to end TB in a generation — including a call for the world to jointly create a new model of research and development to sustain and enhance the existing pipeline of new drugs and ensure treatments are accessible and affordable. The threat of TB was later emphasized during the 45th World Conference on Lung Health also in Barcelona, where the International Union Against Tuberculosis and the Lung Disease and the World Diabetes Foundation warned of a global co-epidemic of diabetes mellitus and TB.

But why has research and development failed to deliver desperately-needed TB treatments for so long, and what are the solutions?

In his speech, British member of the parliament Nick Herbert, co-chairman of the U.K. All-Party Parliamentary Group on TB which co-hosted the event with the IUATLD, highlighted that the commercial structure of pharmaceutical market is largely to blame.

“If this had been a disease that had resurged in the West, we would by now have a new vaccine, rapid testing and better drugs,” he said.

Stop AIDS Advocacy Manager Diarmaid McDonald agrees. More than 95 percent of TB deaths occur in low- and middle-income countries, where pharmaceutical companies do not have the opportunity to make a profit if they invest in treatment.

“In the more than 40 years up to 2013 there were no new TB treatments developed,” McDonald said. “In that same time, there were 14 new treatments developed for hay fever. This great life and death issue is just left to the whim of the market.”

Current anti-TB efforts ‘just a drop in the ocean’

In 2013, a new drug called Bedaquiline was made available for the treatment of multidrug-resistant tuberculosis. This is still in trials and the World Health Organization urges caution in its use. In April this year, a second drug, Delamanid, was also made available for treatment of adults with MDR-TB. Similarly, it is yet to be put through later-stage trials and is unavailable to many groups. McDonald said these developments are welcome, but not enough to tackle the problem.

“It’s just a drop in the ocean in terms of what’s needed,” he explained.

Current MDR-TB treatments involve two years of medication, including eight months of daily injections and more than 14,600 pills to swallow. The medicines have side effects such as deafness, psychosis and severe nausea. Only 48 percent of patients are cured, and in cases of extremely drug-resistant TB, treatment is longer, more expensive and the success rate is only 13 percent.

“There are three or four TB treatment candidates currently in the pipeline at various stages of development and with question marks over their funding,” McDonald emphasized. “When you compare that to something like HIV, you’ve got over a dozen.”

Matt Oliver, APPG TB policy adviser and RESULTS UK health advocacy officer, believes the summit declaration is a step in the right direction.

“We’re going to try and create a framework around which global political will around TB work can be built,” he explains. The elected members represent countries including the U.S., Canada, Brazil, the U.K., France, India, South Africa, Kenya and Tanzania, which plan to collect 100 signatures from other elected representatives from around the world and hold a follow-up meeting in Cape Town, South Africa next year with the G-20.

More DfID commitment needed

The U.K. Department for International Development also needs to lead on gathering cross-government support and investment for reforms to TB R&D, Oliver noted.

“DfID has invested a lot in different types of global R&D through mechanisms like product development partnerships, and supports a lot of front-end research at the academic level through its partnership with the Medical Research Council” he said. “What is lacking is that vocal leadership, and consistent attempts to try and galvanize other donors around a reform model.”

Oliver wants to see innovative approaches to incentivizing new R&D models, such as the advance market commitment DfID agreed with five countries and the Bill & Melinda Gates Foundation in 2007 to develop a vaccine for pneumococcal disease. But before this can happen, he warned that the British aid agency needs to recognize TB treatments as a priority.

Compared to HIV and malaria, DfID contributes considerably less to the prevention and control of TB. In 2012-2013 the department spent an estimated 111.5 million pounds ($176.83 million) on HIV and 90.4 million pounds on malaria in bilateral aid, but only 12.7 million pounds on TB. Similarly, its contribution to the Global Fund to fight AIDS, TB and malaria was 34.5 million pounds for HIV, 71.6 million pounds for malaria and 21.7 million pounds for TB.

A DfID representative told Devex the Global Fund was “the principal mechanism the U.K. uses to finance its contribution to improve access to TB treatment.”

“We also support coordinated action through the Stop TB Partnership and fund research including to develop more effective diagnostics and treatment to tackle TB,” the representative added.

Oliver explained the shortfall in funding is understandable because the department has a limited budget and resources, but called for DfID to develop a long-term strategy to address failures in the R&D model and eliminate TB for good.

Earlier this year, Médecins Sans Frontières launched its proposed solution to the R&D crisis hampering TB treatment. Its Push, Pull, Pool framework aims to revolutionize the funding and coordination of TB R&D to ensure new effective regimens for the disease are rapidly delivered.

The project has three principles: to “push” funding to finance R&D upfront through grants; to “pull” funding to incentivize R&D activities through the promise of financial rewards upon achievement of certain objectives, such as through milestone prizes; and to “pool” intellectual property to ensure open collaborative research and fair licensing for competitive production of final products. Dr. Grania Brigden, MSF TB advisor for the Access Campaign, noted WHO, drug developers, pharmacists and PDPs support the plans.

“They thought it showed real potential to answer some of the specific problems we have with TB,” she said. One of these is that TB treatment involves a combination of drugs. An issue with introducing new treatments has been that they have not been tested alongside other drugs. The 3P model will encourage an open process where drugs are developed in unison, which also reduces duplication.

Financing woes

Another change is the financing model. Brigden says offering milestone prizes will spur research organizations to begin work on potential new drugs. Once these are ready to enter clinical development, more grants and prizes will be offered to ensure drugs continue along the pipeline. Public funding will finance later-stage trials, and at the end treatments will be licensed to multiple manufacturers to ensure prices are kept low.

MSF is currently gathering support for the idea and particularly wants to target middle-income and BRIC countries with high TB-burden that have not historically been very involved with TB R&D.

“This offers a new way for people to come in and fund because they’re paying for the success and the risk element is less,” said Brigden. “There needs to be a substantial amount for the later-stage prize to incentivize probably pharmaceutical companies to come back in and drive the clinical research. But that’s where we see we can move funders, particularly the BRICS: They may be more interested in financing that element of the proposal. Their financing success will have a direct impact into, hopefully, them getting the regimen that addresses their public’s health needs.”

In the meantime, this expert suggests global development professionals lobby their governments to support the 3P proposal and consider ways to fund it.

“We see 3P as a way of using a number of tools that have been used in other areas and putting them all together to ensure we adequately address the problem of TB R&D, because it’s bigger than new drugs,” Brigden said.

Her call echoes that made by Herbert at the Barcelona gathering.

“Political commitment and new resources are needed. The Global Fund provides over 80 percent of all international financing to fight TB. I am proud of 1 billion pound commitment which the U.K. has made to the fund, and many other wealthy countries have also played their full part. But others need to step up to the plate,” he said.  “It's hard for western leaders to commit money at a time of austerity. But quite apart from the moral obligation, TB is a disease that does not recognize national borders. We have a common interest in fighting it.”

Source: Devex Impact