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 The small German-Russian biotech firm which now owns the drug hopes
to confirm its benefits in a mid-stage trial, starting in June, and
then bring in a major pharmaceutical company as a strategic
investor, its chief executive told Reuters.
It is a remarkable turnaround from March 2006, when six healthy
volunteers given the drug in London ended up in intensive care. One
of them was described as looking like "the elephant man" after his
head ballooned. Another lost his fingertips and toes.
The disaster led to the collapse of Germany's TeGenero, the initial
developer of the medicine known as TGN1412.
Since then, however, scientists have developed a way to study the
effects of the drug on human cells in a test tube, allowing the
rational calculation of a safe starting dose.
That has provided a way back into clinical testing for TheraMAB LLC,
a start-up company operating in Germany and Russia, backed by
Moscow-based fund Bioprocess Capital Ventures, which bought the
rights to TGN1412 and renamed it TAB08.
According to an editorial to be published in the next edition of the
British Journal of Clinical Pharmacology, TAB08's "potentially
triumphant return" shows that high-risk medicines can be tested
safely in humans if researchers have detailed insight into how they
work.
"In the course of this disaster a couple of people almost died, the
company (TeGenero) went under and investors lost their money,"
journal editor Adam Cohen of Leiden University told Reuters. "None
of that should have happened."
There is a still a long way to go and the drug may yet fail in
later-stage studies or prove uncompetitive against existing
treatments.
But if successful, its comeback could echo the story of thalidomide,
which caused birth defects when it was launched half a century ago
as a treatment for morning sickness in pregnancy and has now been
repurposed as a treatment for blood cancer.
MONKEY TEST PITFALL
TheraMAB Chief Executive Dmitry Tyrsin said in an interview he had
already discussed the project with more than 20 potential "big
pharma" partners, though any deal would depend on results from the
upcoming mid-stage Phase IIa trial, involving 120 to 150 patients.
That trial has regulatory approval to start in Russia in June and
Tyrsin hopes to get approval to extend it to the United States later
this year. Further off, he aims to test TAB08 in two more autoimmune
diseases, lupus and psoriasis.
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TAB08 is a so-called CD28 superagonist which works by activating
components of the immune system called regulatory T cells, rather
than blocking the system as happens with existing antibody drugs for
rheumatoid arthritis.
That brings a risk of over-stimulation, which is what happened in
the London trial in 2006 when scientists failed to realize that
successful tests on cynomolgus monkeys were not relevant for humans
because of subtle immune system differences.
Now, armed with results from the new lab test, TheraMAB is using
doses that are 10 to 20 times less than in the London study. It has
found early signs of long-lasting benefit in reducing arthritis
symptoms in small initial Phase I tests in people, with no serious
side effects.
In the high-risk biotech industry, the odds of translating such
early success into a commercial product remain low, but Tyrsin
believes the resurrection of TAB08 has wider implications.
"This is good news for the whole industry," he said. "It shows that
if you plan pre-clinical development in the right step-wise way,
then you can safely develop potentially risky drugs."
CD28 superagonists are also being investigated by a number of
academic groups in Europe and Asia for various inflammatory
conditions, as well as stroke and heart disease. None of these
programs has yet been tested in humans.
(Editing by Kate Kelland and Anna Willard)
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