Breakthrough tuberculosis vaccine to start clinical trials
8 June 2010
Archivel Farma, SL has announced that its breakthrough
treatment for tuberculosis (TB) will shortly start phase II clinical
trials. The treatment uses the company’s unique combination of its novel
therapeutic vaccine called RUTI in conjunction with an antibiotic.
It has the potential to cut treatment time from nine months to one
month, which reduces side effects and healthcare costs, by
preventing re-infection during the eradication process.
A major global killer
One third of the world population (2.5 billion) is infected with
Mycobacterium tuberculosis, the bacteria that cause TB in humans.
Every year 100 million people become infected with TB. It is the
second cause of death by infectious diseases after AIDS, claiming a
life every 12 seconds — 2.5 million deaths each year. Infected
people can show no symptoms — latent TB Infection (LTBI) — but 5-25%
will develop active TB at some stage of their life. People with
compromised immune systems are particularly vulnerable such as HIV
patients who have up to 10% risk per year of developing active TB.
Current prevention — one vaccine
The BCG (Bacillus Calmette-Guérin) vaccination has been in use
for 80 years but is only effective at providing infants with
protection against developing disseminated tuberculosis for the
first ten years of their lives. It has little or no effect in
protecting adults, or against pulmonary tuberculosis, the most
common form of the disease.
A LTBI is very hard to treat. It requires a nine month course of
antibiotics which is often not completed because the patient decides
that, as they have no symptoms, they can stop. Not completing the
course means that the bacteria has not been eliminated and can
re-establish. The powerful antibiotics can also have side effects,
such as liver damage, if not closely monitored. A long course is
also logistically challenging especially in third world countries
where TB is endemic.
It has now been discovered that TB does not lie 'dormant' but is
actually waging a constant war with the host, constantly
re-infecting the lungs. Provided that the host is healthy, it has
the upper hand and usually keeps the TB in check.
Mycobacterium tuberculosis is particularly tricky to
eliminate as it can be either replicating, when it can be killed by
the antibiotics, or non-replicating when the antibiotics are not
active against it. The long, nine month course of antibiotics is
needed to ensure that all traces of the non-replicating form are
eliminated from the lungs. Further details can be found at
Reluctance to treat LTBI
Health systems in countries where TB is prevalent are reluctant
to treat LTBI with a nine-month course of antibiotics because
patients can easily become re-infected even if they complete the
course properly as it provides no immunity. Plus there are the costs
and logistics of administering a nine month course. As a result,
there remains a reservoir of TB in the population. What is needed is
an effective, inexpensive way to treat LTBI to reduce the reservoir.
Archivel’s novel two-pronged approach
This combines a one-month course of antibiotic to eliminate the
bacteria in the replicating stage and two injections of the
company’s RUTI vaccine that stimulates the body’s own immune system
to fight the bacteria. This combination approach reduces the
treatment time from nine months to one, is easier to manage, less
expensive, more effective and more likely to done completely. The
company estimates that cost comparison between the current and new
treatment, when allowing for all the logistical costs means that the
new treatment costs around half that of the old treatment.
“We believe that we are the only company to have a solution
targeted specifically at people who have LTBI,” explained Luis
Ruiz-Avila, Archivel’s CEO. “Several vaccines are being developed by
other companies but these tend to focus to either acting as a
booster for people who have had the BCG vaccination or who have not
LTBI. As our solution is quick, easy to administer and inexpensive,
it could be the major step forward required to eliminate TB from the
world’s population by directly tackling the reservoir of TB in
people with LTBI. Migratory flows and Intercontinental jet travel is
ensuring that TB continues to infect people the world over.”
The vaccine RUTI
RUTI is a new polyantigenic vaccine for the treatment of Latent
Tuberculosis Infection (LTBI). It is a therapeutic vaccine, ie it
stimulates an immediate immune response by the body to kill the TB,
but future trials will be required to see if it conveys any lasting
protection from further infections.
It is produced from Mycobacterium tuberculosis, the
strain that actually produces TB, that is fragmented into tiny
particles so there are no live bacteria and detoxified in order to
eliminate the toxic substances produced by the bacteria. The vaccine
RUTI vaccine is the result of the partnership between the
Badalona-based Institut d’Investigació en Ciències de la Salut
Germans Trias i Pujol and Archivel Farma. It has been under
development since the first patent in 2003 with an investment of
more than €10m.
Phase I clinical trials successfully completed
The trial in health volunteers, who did not have LTBI, resulted
in adaptive immunity production indicating that the desired
vaccination effect was achieved without any significant side
Phase II clinical trial to start shortly in South Africa
These trials will determine the safety and immunogenicity of the
anti-tuberculosis vaccine and antibiotic combination for patients
with LTBI. The company expects that this would be followed by
commercial availability in 2015, once its effectiveness will be
proven in a following Phase III trial.
The Medicinal Control Council of the Republic of South Africa
approved on April 22 the start of the first clinical trial of the
therapeutic vaccine RUTI in latent tuberculosis infection (LTBI).
The trial will be run in 3 centres and will enrol 96 individuals
with or without concomitant HIV infection. The primary goal is to
evaluate the safety, tolerability and immunogenicity of the vaccine
RUTI. Primary results are expected by year’s end.
The therapeutic vaccine has already been tested in a double
blind, randomized, placebo-controlled Phase I Clinical trial with 24
healthy volunteers performed in a single site in Catalonia, Spain.
The results, published in the January 22, 2010 issue of the
peer-reviewed journal Vaccine, demonstrated that the
vaccine RUTI is safe, well tolerated and immunogenic, and helped
defining the appropriate dosing and regime to be explored in the
current phase II trial.
Archivel will manufacture and deliver the vaccine RUTI from its
own manufacturing facilities, located in Badalona, close to
Barcelona in Catalonia, Spain. The plant obtained the Spanish GMP
certification in March 2010. It has a built-in P3 lab that enables
the culture and processing of the tuberculosis bacillus (and other
pathogenic agents) in order to produce the final sterile,
lyophilized preparation that does not require any adjuvants.
Initial market for the RUTI vaccine
Archivel believes that the first patients who will benefit from
the vaccine RUTI and antibiotic combination are patients affected by
LTBI with compromised immune systems such as those with HIV or
patients who require anti-TNF-alpha therapies for, say, rheumatoid
arthritis. In the latter case, it is mandatory for them to have the
nine month course to treat LTBI first so a reduction to just one
month with Archivel’s solution is ideal.