The exciting new leprosy treatment that has got scientists talking
An interview with one of the lead researchers, Dr Christian Johnson
The treatment for leprosy has remained consistent for more than 40 years: a combination of antibiotics (Rifampicin, Clofazamine, and Dapsone) that is known collectively as Multi-Drug Therapy (MDT).
When it was endorsed by the WHO for global use in the early 1980s, MDT was the first ever effective cure for one of the oldest diseases on the planet. It was a major breakthrough and over time, it led to a significant drop in the number of cases of leprosy diagnosed each year.
However, MDT has its challenges; it is a very long course of medication, it comes with unpleasant side effects for patients, and there are increasing worries around drug resistance. What’s more, the number of leprosy cases detected each year has stagnated at around 200,000 per year for around a decade. MDT has helped us to reach this milestone, but it is not enough on its own to help us reach any further.
Multi-Drug Therapy is currently the only effective cure for leprosy, but scientists are excited about the potential of a new drug. If it passes the usual test on efficacy and safety, this new drug - Telacebec (Tel-as-a-bec) - could cure leprosy faster and more effectively than anything we have seen before. It could bring about a dramatic change in leprosy transmission, helping us to get over the 200,000 per year hurdle and bring us closer to zero leprosy.
In this article, we talk to Dr Christian Johnson from Fondation Raoul Follereau. Dr Christian is leading global efforts to get Telacebec onto the front lines of the fight to defeat leprosy.
Tim Burton from TLM International: If MDT is an effective cure for leprosy, why do we need a new treatment?
Dr Christian Johnson: Whilst MDT remains the only effective cure for leprosy, it is not without its challenges. The regimen must be taken for between six and 12 months. A patient must take Clofazimine and Dapsone daily, and Rifampicin once a month. Anyone who has taken medication long term knows how easy it is to forget doses or fall out of a habit of taking them.
Beyond this, there are significant challenges for people in remote areas who need to access MDT. It can be a challenge to return to health centres to receive the monthly doses.
All of this reduces the chances that a person will complete their treatment, which is the key to ending transmission and reducing disabilities.
There are further challenges to MDT for patients. Firstly, they may encounter unpleasant side effects. Dapsone can cause anaemia and some patients are hypersensitive to it. Clofazimine has the stigmatising side effect of causing a patients’ skin to darken. This not only marks them out as being affected by a stigmatised disease, it is also a problem in countries where lighter skin is considered a sign of beauty.
Multi-Drug Therapy is effective, but a safer, more effective and shorter treatment could be a game changer.
© Ruth Towell
Tim Burton: Where has Telacebec come from and why is it effective?
Dr Christian Johnson: Telacebec is a drug that has originally come from the world of Tuberculosis. Leprosy is a disease that primarily affects the poorest, so there is not much motivation for scientists and pharmaceutical companies to invest in creating novel drugs to treat leprosy. They will not make money from discovering a new treatment for leprosy and so they are not interested in investing money into finding a new treatment for leprosy. It is a shame, but it is the reality.
Thankfully, there are other ways to find new treatments for leprosy. Because the leprosy and TB bacteria are similar, we look at TB treatments and see if they are effective in leprosy. That is how we have discovered the potential of Telacebec, an antibiotic that has been licensed to the TB Alliance since 2023.
We believe Telacebec will be an effective treatment for leprosy because it does a lot more than the current most effective antibiotic, which is Rifampicin.
Rifampicin is effective because it blocks the duplication of M.leprae, which is the bacteria that causes leprosy. M.leprae is a slow moving bacteria and only multiplies once every two weeks, which is why patients take Rifampicin once a month.
Telacebec has a different mechanism of action. Instead of blocking duplication of M.leprae, Telacebec prevents the bacteria from receiving the energy it needs. It is effectively like putting a glass over a flame; without the oxygen the flame will go out and without energy, the M.leprae will die.
Nature’s gift to all living organisms is a large network of redundancy plans for the systems that keep us all alive. When one option is not viable, nature finds an alternative. For example, in the TB bacteria, Telacebec cuts off the bacteria’s access to energy, but the bacteria is able to find a new route to access energy. Telacebec slows the TB bacteria down, but it does not stop it.
However, leprosy is one of the oldest diseases on the planet. Over the millennia that M.leprae has been on this planet, it has lost a lot of its genes. This means that Telacebec cuts off the bacteria’s access to energy and it is not able to find an alternative route to access the energy it needs.
What we have seen so far is that Telacebec will kill the M.leprae within a person’s body with just one or two doses. That is unheard of with leprosy.
If our planned studies are conclusive, it will be possible to develop a novel Telacebec-based MDT treatment regimen that is safer, shorter, and consists of fewer drugs with the possibility of eliminating the need for daily dosing.
Another piece of good news is that early evidence suggests that Telacebec will also be effective in the treatment of Buruli Ulcer.
Tim Burton: What stage are your planned studies at?
Dr Christian Johnson: There are four stages to proving the efficacy of a new drug. You start with a preclinical study, which means lab testing. The next step is Phase 1 of the clinical trials, where we administer the drug to a small number of healthy individuals to see if it causes any side effects. Because Telacebec has come from the TB world, it has already been through much of this process. There have been some mild side effects, but nothing particularly worrying.
Phase 2 of the clinical trials are about efficacy and safety. The new treatment is tested on a very small number of infected individuals and the results and side effects are carefully monitored. This is the stage that we are hoping to start soon with Telacebec.
© Tom Bradley
Phase 3 would then be a Randomised Controlled Trial, the purpose of which would be to demonstrate efficacy and safety in a large number of patients. After this stage, you can submit your documentation for the new treatment to be officially approved.
We see ILEP Members as crucial partners in this effort and so we presented a case for funding that will help us to finalise the preclinical studies to support the Phase 2 trial. Thankfully they accepted that proposal in recent weeks, including funding from TLM.
We have also applied to the European Union for funding to run a Phase 2 trial for leprosy and Phase 3 trial for Buruli ulcer. If we are successful, a trial will begin in Ethiopia, the Ivory Coast, and Benin.
Leprosy is a slow moving disease, which means new treatments are not found quickly. Fast moving diseases like Covid-19 mean that, with the right resources, scientists can find vaccines and treatments quickly. I want to set expectations that this will take longer because leprosy moves so slowly.
Our plan is that the Randomised Controlled Trial will take between five and seven years.
Throughout this time, we will test a variety of Telacebec-based MDT regimens. Although Telacebec is far more effective than anything we have seen previously, we still believe that a multi-drug regimen is appropriate, as it reduces the risk of drug resistance.
Tim Burton: What challenges are you expecting to face and how can the wider leprosy community support you?
Dr Christian Johnson: Running a Randomised Controlled Trial is very expensive. You have to mobilise staff, labs, and governments over a period of five or more years.
The most effective way for The Leprosy Mission and other ILEP Members to help is to maintain momentum behind this project.
Maintaining momentum means mobilising donors who believe leprosy is important. We need to inform them that if we have more resources, we can overcome this disease. We need resources for detection, management of patients, and for research to develop new tools for leprosy control.
We need the support of donors and we need the support of governments. TLM and other ILEP partners can be crucial in providing this support.
Tim Burton: What is your great hope for Telacebec?
Dr Christian Johnson: My hope is that patients will finally have a treatment that is fast, safe, and effective. My hope is that we, as a leprosy sector, will have a treatment and a new preventative medication that will allow us to dramatically cut the transmission of leprosy across the world.
If Telacebec is as effective as it seems to be, we may see the kind of sea change that we saw when MDT was first introduced, as the number of leprosy cases worldwide drops dramatically. That is my hope for Telacebec.
