Dr Mel Spigelman is the President and Chief Executive Officer of the Global Alliance for TB Drug Development (TB Alliance). He is a leader in developing a regimen-based paradigm of TB drug development – a faster and more efficient approach, which is emerging as the gold standard within the TB drug research field. A recipient of the American Cancer Society’s Clinical Oncology Career Development Award (1985-1988), Dr Spigelman is presently the Co-Chair of the Working Group on New Drugs of the WHO Stop TB Partnership. Edited excerpts from an interview with FM
Can you kindly brief us on the current status of TB Alliance’s TB clinical programmes?
TB Alliance is conducting three late-stage clinical trials to evaluate new drug regimens for various forms of TB. Two of the trials, known as Nix-TB and ZeNix, are evaluating three-drug (bedaquiline+ pretomanid+ linezolid), six-month regimens for the most resistant cases of TB, including XDR-TB. Another trial, called SimpliciTB, is evaluating a four-drug – bedaquiline + pretomanid+ moxifloxacin+ pyrazinamide – regimen to treat both drug-sensitive TB in four months and multidrug-resistant TB in six, respectively.
What are the latest drug regimens to tackle MDR/XDR TB?
The World Health Organization recently released new treatment guidelines for treating drug-resistant TB. Currently, the recommended treatment duration ranges from about 9 to 20 months. For the longer treatment regimens, WHO no longer prioritises the use of injectable drugs in the treatment of drug-resistant TB. There are multiple different regimens in a variety of clinical trials, including STREAM, TB-PRACTECAL, endTB and NeXT in addition to the trials sponsored by TB Alliance.
Multi-drug resistance poses a formidable challenge to bring TB pandemic under control. How does TB Alliance strategize to deal with this growing threat?
Our strategy is to develop novel TB drug regimens that are shorter, safer, more effective and affordable. Treatments with those characteristics could both cure people with drug-resistant TB and prevent resistance from emerging in the first place. A strong pipeline of novel drugs will ensure that we are well-prepared to treat any form of the disease, which will be essential to meeting global and national targets for TB eradication.
In what ways does TB Alliance address the question of affordability of the new TB regimens in the developing world where TB is a major healthcare problem?
In line with our “AAA” mandate, we are committed to ensuring that all drugs and regimens we work on will be affordable, available and adopted around the world. We de-risk the research and development of our work through the financial support from our donors, which lowers the bar for our commercial partners to get involved. We also ensure that all molecules in which we invest can be manufactured at a very reasonable cost of production. In addition, we will give royalty-free licenses to our products to multiple, high-quality manufacturers in the developing world to generate generic competition. Through generic competition, as we have seen in many fields, prices can be reduced to their lowest sustainable levels.
One of the stated goals of TB Alliance is making ultra-short, simple treatment regimens for battling TB. How far has the organization succeeded in achieving this objective?
We have developed the largest single portfolio of potential new TB therapeutics ever assembled. Our goal is to discover or partner with others on multiple new chemical entities that do not have cross-resistance with presently available anti-TB drugs, and which can be given together in regimens that are safe enough to be used in all TB patients and effective enough to dramatically shorten the duration of TB therapy. We now have multiple new drug candidates in our pipeline that, in combination with those of other organisations, have the potential to deliver a very short treatment for virtually all patients with active TB.
What is TB Alliance’s most crucial therapeutic intervention in TB management?
Children with TB have long been the neglected of the neglected, with an estimated 1 million children developing TB each year. To date, we have seen major progress in the global uptake of child-friendly TB medicines introduced by TB Alliance and our partners, with
over 900,000 treatment courses ordered by 88 countries and counting since becoming available at the end of 2015. These new formulations of first-line treatment, which are available in India, come in WHO-approved doses and are designed to be easy for children to take: fruit flavoured for palatability and dissolvable in water. Looking ahead, we hope to introduce novel TB drug regimens that are shorter, safer, effective and affordable, suitable for every person with TB.