D
euteration is often defined as a process of
improving pharmacokinetic property of drug by
replacing one or more hydrogen with deuterium
(an isotopic form of hydrogen). It is believed that by
replacing a few hydrogen atoms with deuterium, rate of
metabolic breakdown of the drug is reduced and the drug
is absorbed to a greater extent in human body. Taking
these drugs lead to lower dosage of medication. Perhaps,
deuterium-carbon bonds are generally about six to 10
times more stable than the corresponding hydrogen-
carbon bond. These stronger bonds are more difficult to
break, which can slow the rate of bond cleavage
Deuterated drugs are gaining attention by scientific
community when issues such as patent cliff, drug
shortages, high costs, and chronic disorders are
crippling pharmaceutical industry. Pharma firms like
Merck, Pfizer, had previously explored clinical benefits
of deuterated versions of existing drugs but they have
faced approval hurdles. For eg, Fludalanine (2-deutero-
3-fluoro-D-alanine), an antibacterial agent developed
by Merck, was unsuccessful to show effectiveness
under preclinical studies. The concept of remodelling
older drugs raises eyebrows in the industry. Companies
reshape older drugs to improve them and gain new
market exclusivity without investing in the roots of a new
drug. Sometimes, it raises questions that a company has
not done R&D for a drug.
In contrast, pharma giants such as Teva, Concert,
and Celgene are knocking on the doors of patent
rights for their deuterated innovation. Recent FDA
approval to the world’s first deuterated drug developed
by Teva has shaken pharmas. The drug is a modified
version of the generic tetrabenazine. It was designed
to treat the involuntary movements caused by the fatal
neurodegenerative condition Huntington’s disease. Not
well-tolerated by some patients, it has to be taken more
frequently than deutetrabenazine.«
Sakshi Sharma
Market Research
Analyst, ClearsynthBeating bug with
deuterated drugs
The drug modification
could address patent
cliff, drug shortages,
high costs and chronic
disorders issuesConcert Pharmaceuticals would also soon prove
itself as leader in deuteration. The company has
developed deuterated chemical entity (DCE) Platform®
technology. It has recently presented Phase I results on
CTP-347, a selectively deuterated analogue of paroxetine
for the treatment of hot flashes. It’s another candidate
CTP-518, an HIV protease inhibitor (PI) based on the
atazanavir scaffold, is under trial. Several other potential
novel deuterated drugs have entered clinical evaluation.
Auspex Pharmaceuticals (a part of Teva) is
developing SD-254, a selectively deuterated analogue
of antidepressant venlafaxine. Berolina innovative
Research and Development Services Pharma (BiRDS
Pharma) is developing BDD-10103, a deuterated analog
of muscle relaxant tolperisone. Well-known name in
drug discovery, Celgene has announced collaboration
with Concert Pharma to create new deuterium-modified
small molecule compounds targeting cancer and
inflammation.According to experts, market of deuterated drugs
is anticipated to be worth US$ 1billion. To support
pharma industry in deuterium research, several custom
synthesis companies like CDN isotopes, Clearsynth Labs,
Cambridge Isotopes etc. provide d-labelled reagents,
intermediates, building blocks of final APIs for such
studies. It is not surprising that Teva’s deuterated drug
approval would mark a big plus for many other products
under trials.
World’s first approval would encourage innovation
and new players in the deuterium industry. However,
investors and players have to focus on cost, awareness
and new combinations. We see a bright future of
deuterated drugs though it demands lots of investment
as well as acceptance by regulatory agencies.(^48) BIOTalk BioSpectrum | May 2017 | http://www.biospectrumindia.com