Cepheid, a Sunnyvale, Calif.-based molecular diagnostics company, FIND, a Switzerland-based international nonprofit organization and Rutgers New Jersey Medical School are collaborating to develop Xpert MTB/RIF Ultra, a next-generation test for Mycobacterium tuberculosis (TB) with increased sensitivity to aid in detection of patients with smear-negative TB, which often is associated with HIV co-infection. The collaboration also is receiving additional support from the National Institute of Allergy and Infectious Diseases at the NIH.

Technological innovations will leverage the power of Cepheid's GeneXpert System, currently the only platform for near-patient molecular TB testing. Over 7,500 GeneXpert Systems are deployed globally, including over 3,500 installed in 110 high burden developing countries (HBDC), making it the most widely distributed molecular platform in the world. Xpert MTB/RIF Ultra will run on existing six color GeneXpert Systems and is expected to be provided to HBDC markets at the same price as Xpert MTB/RIF.

"There is a pressing need for continued innovation in the field of TB diagnostics. The low sensitivity of smear microscopy limits its impact on TB control," said Dr. Catharina Boehme, CEO of FIND. "Xpert MTB/RIF Ultra has great potential to transform the way we diagnose the three million people who every year fail to receive TB testing or treatment. We are proud to partner with Cepheid in launching this highly sensitive and rapid test that will identify even more patients than its predecessor and make quality diagnostics a reality for people in the developing world."

"One reason that Xpert MTB/RIF has been heralded as a game-changer is its capability to detect individuals with infection. However, low levels of organisms are especially prominent in patients coinfected with HIV. These patients are commonly referred to as smear-negative because traditional microscopy does not detect their TB infection," said John Bishop, Cepheid's chairman and CEO. "An ability to identify these patients with an extremely high level of sensitivity with a single test represents a significant step forward in what already has been hailed worldwide as a revolutionary advance in the diagnosis of TB."

A primary reason current tests have difficulty identifying early-stage TB is that the target DNA in patient samples is below the levels of test detection. The Xpert MTB/RIF Ultra collaborative team plans to capitalize on Cepheid's unique, cartridge-based nested PCR amplification capability to amplify patient DNA samples to a level that can be more accurately detected. The current Xpert MTB/RIF test has a limit of detection (LOD) of 130cfu/ml.

New innovations, including a larger DNA reaction chamber in the cartridge, will enable Xpert MTB/RIF Ultra to bring the LOD down ten-fold, to approximately10cfu/ml (across all strains)—a level similar to or potentially better than liquid culture.

"The data clearly show that TB still is treated empirically in primary care settings because clinicians fear that a negative test result only means that the disease is not advanced enough to be detected. In addition, some serious cases of TB can be smear negative because a patient has a poor cough or is HIV positive," said David Alland, M.D., professor and chief, division of infectious diseases, Center for Emerging Pathogens at Rutgers New Jersey Medical School. "There is a huge need for an on-demand test that can accurately identify individuals with early-stage TB who currently test negative with other tests. Our preliminary results strongly suggest that Xpert MTB/RIF Ultra will not only eliminate the need for empiric therapy, it will cut TB treatment costs in half."

Cepheid also is developing an additional test to specifically call out extensively drug-resistant (XDR) tuberculosis. XDR TB is a form of multidrug-resistant tuberculosis (MDR TB) that is resistant to the most potent TB drugs—isoniazid, rifampin, aminoglycosides and any fluoroquinolone.

"When it comes to detecting TB, poor sensitivity for poor countries is not a winning combination," said David Persing, M.D., Ph.D., Cepheid's chief medical and technology officer. "Our collaboration with Dr. Alland and FIND to create Xpert MTB/RIF has truly helped revolutionize TB care around the world. Millions of people currently receive effective TB care each year—but missed cases are stalling gains. This new product will help to eliminate guesswork and deliver maximum medical impact in the management of TB cases worldwide."

Xpert MTB/RIF Ultra is expected to be available to the HBDC market in the first half of 2016.